VA/DoD CLINICAL PRACTICE GUIDELINE FOR 

THE DIAGNOSIS AND MANAGEMENT OF 

HYPERTENSION 

IN THE 

PRIMARY CARE SETTING

Department of Veterans Affairs

Department of Defense

QUALIFYING STATEMENTS

The Department of Veterans Affairs and the Department of Defense guidelines are based upon the best 

information available at the time of publication. They are designed to provide information and assist 

decision-making. They are not intended to define a standard of care and should not be construed as 

one. Neither should they be interpreted as prescribing an exclusive course of management. 

This Clinical Practice Guideline is based on a systematic review of both clinical and epidemiological 

evidence. Developed by a panel of multidisciplinary experts, it provides a clear explanation of the logical 

relationships between various care options and health outcomes while rating both the quality of the 

evidence and the strength of the recommendations. 

Variations in practice will inevitably and appropriately occur when clinicians take into account the needs 

of individual patients, available resources, and limitations unique to an institution or type of practice. 

Every healthcare professional making use of these guidelines is responsible for evaluating the 

appropriateness of applying them in the setting of any particular clinical situation.

These guidelines are not intended to represent TRICARE policy. Further, inclusion of recommendations 

for specific testing and/or therapeutic interventions within these guidelines does not guarantee 

coverage of civilian sector care. Additional information on current TRICARE benefits may be found at 

www.tricare.mil or by contacting your regional TRICARE Managed Care Support Contractor

Version 3.0 – 2014
October 2014 Page 2 of 135

Prepared by:

The Diagnosis and Management of Hypertension

Working Group

With support from:

The Office of Quality, Safety and Value, VA, Washington, DC

& 

Clinical Performance Assurance Directorate, United States Army MEDCOM

Version 3.0 – 2014 

Based on evidence reviewed through April 2014 
October 2014 Page 3 of 135

Table of Contents

Table of Contents................................................................................................................................................... 3

Background............................................................................................................................................................ 5

About this Clinical Practice Guideline (CPG)........................................................................................................... 6

Scope of this CPG................................................................................................................................................... 6

Population ................................................................................................................................................................. 7

Intervention............................................................................................................................................................... 7

Key Differences in This Guideline Update .............................................................................................................. 7

Methods................................................................................................................................................................ 8

Reconciling 2004 Guideline Recommendations......................................................................................................... 9

Algorithm Format....................................................................................................................................................10

Patient-Centered Care .............................................................................................................................................11

Implementation.......................................................................................................................................................12

Guideline Working Group .................................................................................................................................... 13

Algorithm ............................................................................................................................................................ 14

Recommendations............................................................................................................................................... 16

Screening, Diagnosis and Measurement of Hypertension.................................................................................... 21

Screening................................................................................................................................................................. 21

Diagnosis................................................................................................................................................................. 22

Measurement Techniques.......................................................................................................................................26

Adherence to Therapy ......................................................................................................................................... 29

Lifestyle Modification Therapies.......................................................................................................................... 31

Weight Reduction....................................................................................................................................................31

Exercise/Physical Activity ........................................................................................................................................32

Mind-body Therapies...............................................................................................................................................33

Dietary Modification ...............................................................................................................................................33

Sodium Reduction....................................................................................................................................................35

Alcohol Reduction....................................................................................................................................................37
October 2014 Page 4 of 135

Pharmacological Therapy..................................................................................................................................... 37

Initiation of Pharmacotherapy ................................................................................................................................37

Blood Pressure Goals...............................................................................................................................................40

Hypertension Control and Follow-up.......................................................................................................................44

Monotherapy or Combination Therapy...................................................................................................................48

First-line Therapy.....................................................................................................................................................49

Alternative or Supplementary Therapies.................................................................................................................51

Specific Populations.................................................................................................................................................54

Appendix A: Evidence Review Methodology........................................................................................................ 60

Conducting the Systematic Review..........................................................................................................................60

Inclusion and Exclusion Criteria...............................................................................................................................64

Outcomes ................................................................................................................................................................64

Literature Search Strategies....................................................................................................................................65

Convening the Face-to-Face Meeting....................................................................................................................101

Grading Recommendations...................................................................................................................................101

Drafting and Submitting the Final CPG .................................................................................................................104

Appendix B: Evidence Table............................................................................................................................... 105

Appendix C: Dietary Information ....................................................................................................................... 113

Appendix D: Blood Pressure Thresholds to Initiate Pharmacologic Therapy and Treatment Goals .................... 114

Appendix E: Drug Dosage Table ......................................................................................................................... 115

Appendix F: Participant List ............................................................................................................................... 118

Appendix G: Acronyms List ................................................................................................................................ 119

References......................................................................................................................................................... 122
October 2014 Page 5 of 135

Background

This guideline developed under the auspices of the Veterans Health Administration (VHA) and the 

Department of Defense (DoD) pursuant to directives from the Department of Veterans Affairs (VA) is an 

update to the 2004 VA/DoD Clinical Practice Guideline for Diagnosis and Management of Hypertension 

in the Primary Care Setting. 

Hypertension (HTN) is clinically defined as a systolic blood pressure (SBP) >140 mmHg or a diastolic 

blood pressure (DBP) of >90 mmHg. Prehypertension is classified as SBP 120-139 or DBP 80-89. The 

Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of 

High Blood Pressure (JNC 7) went on to further classify hypertension into stages [1] (Stage 1: SBP 140-

159 mmHg or DBP 90-99; Stage 2: SBP >160 mmHg or DBP >100 mmHg), though the use of these stages

has begun to be phased out. Hypertension is usually asymptomatic; therefore, routine screening is 

important in order to diagnose the condition. Also, because patients will mostly likely not feel 

symptoms, the asymptomatic nature of hypertension can lead to challenges with adherence to 

treatment. 

Patients with hypertension either have primary or secondary hypertension. Primary, or essential, 

hypertension accounts for about 95% of cases and is a heterogeneous disorder in which different causal 

factors, including genetic predisposition, central adiposity, sedentary lifestyle, and dietary choices, can 

lead to high blood pressure. [2] Secondary hypertension is high blood pressure that results from an 

underlying and identifiable cause. [3] Main causes of secondary hypertension include adverse effects of 

medications, tobacco products or illegal drugs, renal disease, obstructive sleep apnea, 

pheochromocytoma, aldosteronism, and aortic coarctation. 

Complications of hypertension include damage to the large arteries (macrovascular complications) that 

can lead to stroke, myocardial infarction (MI), or peripheral arterial diseases, as well as damage to the 

smaller arteries (microvascular complications) that can lead to chronic kidney disease (CKD) or 

retinopathy. In addition to these arterial complications, hypertension by itself can lead to left ventricular 

hypertrophy (LVH) and chronic heart failure (CHF), another frequent cause of death in the United States 

(US). 

In the US, about 77.9 million adults (one out of every three) have hypertension. Of those only 81.5% are 

aware of their condition, 74.9% are undergoing treatment, and just over half (52.5%) have their 

hypertension controlled. [4] Uncontrolled hypertension has been shown to be higher in older 

Americans, non-Hispanic blacks and individuals with certain co-morbid conditions, including diabetes 

and CKD. [5] 

In a 2008 study, it was found that 13% of active duty Service Members had hypertension, the majority of 

whom were <40 years of age. [6] It was reported that, as in the civilian population, increased age, 

increased body mass index (BMI), male sex, black race/ethnicity, and senior rank were all independently 

associated with hypertension. Another study surveyed active duty Service Members at baseline (2001-

2003) and then again after three years (2004-2006) and found that while military personnel who were 

deployed had a lower incidence of hypertension in general than those who were not deployed, 
October 2014 Page 6 of 135

deployment with multiple stressful combat exposures was an independent risk factor for newly reported 

hypertension. [7] Over 37% of Veterans have hypertension, making it the most common chronic medical

condition among Veterans. [8] The control of hypertension, however, has significantly improved among 

Veterans. While only 45.7% of Veterans had their blood pressure controlled in 2000, by 2010, the rate 

had improved to 76.3%. [9] 

This clinical practice guideline (CPG) on the management of HTN in the primary care setting is intended 

to promote evidence-based management of hypertension and thereby improve patient’s clinical 

outcomes. It can assist primary care providers or specialists in the screening and diagnosis of HTN, 

determination of appropriate treatment, and delivery of individualized interventions. Although it was 

developed for a broad range of clinical settings, it should be applied with enough flexibility to 

accommodate local practice and individual situations. 

About this Clinical Practice Guideline (CPG)

The VA/DoD CPG for the Diagnosis and Management of Hypertension in the Primary Care Setting is 

intended to assist healthcare providers in all aspects of outpatient care for patients with hypertension. 

The system-wide goal of evidence-based guidelines is to improve the patient’s health and wellbeing. The 

overall expected outcome of successful implementation of this guideline is to:

• Formulate an efficient and effective assessment of the patient's condition

• Optimize the use of therapy to reduce symptoms and enhance functionality

• Minimize preventable complications and morbidity

• Emphasize the use of personalized, proactive, patient-driven care

This guideline represents a significant step toward achieving these goals for patients in the VA and DoD. 

However, as with other CPGs, remaining challenges involve developing effective strategies for guideline 

implementation and evaluating the effect of guideline adherence on clinical outcomes.

The guideline is not intended to serve as a standard of care. Standards of care are determined on the 

basis of all clinical data available for an individual case and are subject to change as scientific knowledge 

and technology advance and patterns evolve. The guideline is based on information available at the date 

of publication, and is intended to provide a general guide to best practice. However, it should be 

emphasized that evidence-based clinical practice involves using the best available research evidence, 

but also exercising the practitioner’s clinical judgment to take into account individual patient indicators 

and preferences. The guideline can assist healthcare providers, but the use of a CPG must always be 

considered as a recommendation, within the context of a provider’s clinical judgment, in the care of an 

individual patient.

Scope of this CPG

This CPG is designed to assist primary care providers in identifying and managing patients with 

hypertension. The target audience of the CPG is VA/DoD and other primary care physicians who 
October 2014 Page 7 of 135

treat active duty, reserve, National Guard and retired military personnel and their adult family 

members. The CPG addresses the following elements:

Population

The patient population of interest for this CPG is adults (men and women) who are eligible for care in 

the VA and DoD healthcare delivery systems. It includes Veterans as well as deployed and non-deployed 

active duty Service Members. This CPG does not provide recommendations for the management of 

hypertension in pregnant women, peri-operative/inpatient adults, children or adolescents.

Intervention

This CPG addresses various management strategies for patients with hypertension. This includes 

assessing the benefits and harms associated with antihypertensive pharmacologic therapies as well as 

the blood pressure thresholds to initiate therapy and appropriate blood pressure targets. In addition to 

primary care provider pharmacological management strategies, the CPG discusses the impact of nonpharmacologic therapies (e.g., weight reduction, sodium reduction, physical activity) on improving 

hypertension management. The CPG also reviews what measurement techniques are the best indicators 

to initiate hypertension therapy. 

Key Differences in This Guideline Update

This document is an update of the 2004 clinical practice guideline on the Diagnosis and Management of 

Hypertension in the Primary Care Setting. As such, there are aspects of this guideline that have been 

modified from the previous version based on new evidence and the current Guideline Work Group’s 

interpretation of the clinically appropriate scope of the guideline. Clinicians may find that this updated 

VA/DoD guideline has recommendations that differ from recommendations generated by other groups 

that have published guidelines on the management of hypertension. For example, this updated VA/DoD 

guideline recommends using particular blood pressure thresholds for initiating pharmacologic therapy 

and blood pressure goals that differ from other published guidelines. These differences may derive in 

part from differences in the basis for guideline development. For this guideline, the Guideline Work 

Group first developed key research questions to examine available evidence pertaining to the optimal 

blood pressure thresholds for initiating pharmacotherapy and the available evidence pertaining to 

optimal goals for treating blood pressure. The systematic evidence review also addressed systolic and 

diastolic thresholds and goals independently. Based on the evidence for treatment initiation thresholds 

and the evidence for treatment goals, the Guideline Work Group recommends SBP thresholds and goals 

that are somewhat higher than those to which many clinicians have been accustomed. 

Another way in which this guideline tends to differ from some other recently published guidelines is that 

it is less inclusive of drug classes recommended for first-line therapy. This guideline recommends using 

thiazide-type diuretics as first-line therapy and then proceeds to recommend certain other drug classes 

for supplemental therapy as clinically indicated. The recommendation pertaining to first-line therapy is 

based on the totality of evidence, including numerous placebo controlled trials, and in part on the 

Guideline Work Group’s determination from the available evidence that findings of many clinical trials 

that have supported drug classes other than thiazide-type diuretics as first-line therapy did not use 
October 2014 Page 8 of 135

optimal doses of thiazides for reducing adverse cardiovascular and cerebrovascular outcomes in their 

control groups. 

The guideline update also uses a different system to evaluate evidence than the 2004 version. This 

guideline uses the Grading of Recommendations Assessment, Development and Evaluation (GRADE) 

method for appraising the quality of a body of evidence and creating evidence-based recommendations. 

The GRADE system began to be developed in 2000 and many US and international organizations have 

provided input into the development of the approach and endorsed it. Among those that are using it (or 

near modifications of it) are: the Agency for Healthcare Research and Quality Evidence-based Practice

Centers, Centers for Disease Control and Prevention advisory panels, Cochrane Collaboration, Kaiser 

Permanente, National Institute for Health and Care Excellence (United Kingdom[UK]), National Kidney 

Foundation Kidney Disease Outcomes Quality Initiative, World Health Organization, and medical 

professional societies (e.g., American College of Chest Physicians, American College of Physicians, 

American Gastroenterological Association, Canadian Cardiovascular Society, The Endocrine Society, and 

Society of Critical Care Medicine). Further information on evaluating evidence and developing 

recommendations using the GRADE method can be found in the Grading Recommendations section. 

Compared to the 2004 version of the VA/DoD guideline, clinicians will notice that the Guideline Work 

Group has added recommendations, based on literature published in the last several years, pertaining to 

the use of home blood pressure monitoring (HBPM) and ambulatory blood pressure monitoring (ABPM) 

to confirm the diagnosis of hypertension though HBPM and ABPM are not currently in widespread use 

for that purpose. Also, many recommendations pertaining to managing hypertension with certain highly 

prevalent comorbid conditions were not carried forward to this version of the guideline. The Guideline 

Work Group determined that those topics were out of scope for this guideline, as they are largely 

covered in the VA/DoD clinical practice guidelines for diabetes mellitus,1 chronic kidney disease,2 and 

chronic heart failure.3

 

Methods

The methodology used in developing the 2014 CPG follows the Guideline for Guidelines, [10] an internal 

document of the VA and DoD Evidence-Based Practice Working Group (EBPWG). This document 

provides information regarding the process of developing guidelines, including the identification and 

assembly of the Guideline Champions (Champions) and other subject matter experts from within the VA 

and DoD, known as the Work Group, and ultimately, the submission of an updated HTN CPG.

1 See the VA/DoD Clinical Practice Guideline for the Management of Diabetes Mellitus in Primary Care. Available 

at: http://www.healthquality.va.gov/guidelines/CD/diabetes/index.asp 2 See the VA/DoD Clinical Practice Guideline for the Management of Chronic Kidney Disease. Available at: 

http://www.healthquality.va.gov/guidelines/cd/ckd/index.asp

3 See the VA/DoD Clinical Practice Guideline for the Management of Chronic Heart Failure. Available at: 

http://www.healthquality.va.gov/guidelines/cd/chf/index.asp
October 2014 Page 9 of 135

The Champions and Work Group for this CPG were charged with developing evidence-based clinical 

practice recommendations and publishing a guideline document to be used by providers within the 

VA/DoD healthcare system. Specifically, the Champions for this guideline were responsible for 

identifying the key questions of greatest clinical relevance, importance and interest for the diagnosis 

and management of patients with HTN. In addition, the Champions assisted in:

1. Conducting the evidence review, including providing direction on inclusion and exclusion

criteria;

2. Assessing the level and quality of the evidence;

3. Identifying appropriate disciplines to be included as part of the Work Group;

4. Directing and coordinating the Work Group; and

5. Participating throughout the guideline development and review processes.

The VA Office of Quality, Safety and Value, in collaboration with the Clinical Performance Assurance 

Directorate, Office of Evidence-Based Practice, US Army Medical Command, the lead agency for the 

DoD, identified two clinical leaders, Dr. William Cushman from VA and Dr. Travis Harrell from DoD, as 

Champions for the 2014 HTN CPG. 

The Lewin Team (Team), including DutyFirst Consulting, was contracted by VA and DoD to support the 

development of this CPG and conduct the evidence review. The Team held the first conference call in 

September 2013, with participation from the contracting officer’s representatives (COR), leaders from 

the VA and DoD evidence-based guideline development program, and the Champions. During this call, 

the project team discussed the scope of the guideline initiative, the roles and responsibilities of the 

Champions, the project timeline, and the approach for developing specific research questions on which 

to base a systematic review about the diagnosis and management of HTN. The group also identified a list 

of clinical specialties and areas of expertise that are important and relevant to the diagnosis and 

management of HTN, from which the Work Group members were recruited. The specialties and clinical 

areas of interest included: Primary Care, Internal Medicine, Nursing, Pharmacy, Dietetic and Nutritional 

Services, Geriatrics, and Physical Therapy.

The guideline development process for the 2014 CPG consisted of the following steps:

1. Formulating evidence questions (Key Questions);

2. Conducting the systematic review;

3. Convening a three and a half day face-to-face meeting with the CPG Champions and Work

Group members; and

4. Drafting and submitting a final CPG on the management of HTN to the VA/DoD EBPWG.

Appendix A provides a detailed description of each of these tasks.

Reconciling 2004 Guideline Recommendations

Evidence-based CPGs should be current, which typically requires revisions based on new evidence, or as 

scheduled, subject to time-based expirations. For example, the U.S. Preventive Services Task Force

(USPSTF) has a process for refining or otherwise updating its recommendations pertaining to preventive 
October 2014 Page 10 of 135

services. [11] Further, the inclusion criteria for the National Guideline Clearinghouse specify that a 

guideline must have been developed, reviewed or revised within the past five years. 

The HTN Guideline Work Group focused largely on developing new and updated recommendations 

based on the evidence review conducted for the priority areas addressed by the key questions. In 

addition to those new and updated recommendations, the Guideline Work Group considered the 

current applicability of other recommendations that were included in the previous CPG on management 

of HTN, published in 2004, subject to evolving practice in today’s environment. Subject to Guideline 

Work Group consensus, recommendations that were no longer relevant to the current practice 

environment, or were otherwise out of scope for this CPG, were not carried forward to this CPG. 

Recommendations that were considered to be relevant to the current practice environment and still in 

scope for this CPG, and that required no substantive (i.e., entailing clinically meaningful) rewording, 

were carried forward in this CPG. The wording was, however, modified slightly to be best utilized in 

today’s clinical environment and to uphold the GRADE recommendation format. (For more information 

on GRADE methodology, please refer to Grading Recommendations in Appendix A.) For some modified 

recommendations, the Guideline Work Group referred to the available evidence as summarized in the 

body of the 2004 CPG, though not all of these were the object of a systematic evidence review for the 

2004 CPG. Some modified recommendations carried forward from the 2004 HTN CPG, however, were 

based on an updated systematic review conducted since the 2004 HTN CPG due to the topic being a 

priority area addressed by the key questions. These “modified” recommendations, and whether or not 

an updated systematic review was conducted, are noted in the list on page 16. 

The Guideline Work Group recognized the need to accommodate the transition in evidence rating 

systems from the 2004 CPG to the current CPG. In order to report the strength of all recommendations 

using a consistent format (i.e., the GRADE system), the Guideline Work Group converted the USPSTF 

strengths of the recommendation accompanying the carryover recommendations from the 2004 

guideline to the GRADE system. As such, the Guideline Work Group considered the strength of the 

evidence cited for each recommendation in the 2004 CPG as well as harms and benefits, values and 

preferences, and other implications, where possible. In some instances, peer-reviewed literature 

published since the 2004 CPG was considered along with the evidence base used for that CPG. Where 

such newer literature was considered when converting the strength of the recommendation from the 

USPSTF to GRADE system, it is noted in the discussion that follows the corresponding recommendation.

The Guideline Work Group recognizes that, while there are practical reasons for incorporating findings 

from a previous systematic review or previous recommendations [12] or recent peer-reviewed 

publications into an updated CPG, doing so does not involve an original, comprehensive systematic 

review and therefore may introduce bias. 

Algorithm Format

This CPG includes an algorithm, which is designed to maximally facilitate clinical decision-making for the 

diagnosis and management of HTN. The use of the algorithm format was chosen based on the 

understanding that such a format can allow for diagnostic and therapeutic decision-making, and has the 
October 2014 Page 11 of 135

potential to change patterns of resource use. The algorithm format allows the provider to follow a linear 

approach to critical information needed at the major decision points in the clinical process. It includes:

• An ordered sequence of steps of care

• Recommended observations

• Decisions to be considered

• Actions to be taken

A clinical algorithm diagrams a guideline into a step-by-step decision tree. Standardized symbols are 

used to display each step in the algorithm, and arrows connect the numbered boxes indicating the order 

in which the steps should be followed. [13] 

Rounded rectangles represent a clinical state or condition.

Hexagons represent a decision point in the guideline, formulated as a question 

that can be answered Yes or No. 

Rectangles represent an action in the process of care.

Ovals represent a link to another section within the guideline.

Patient-Centered Care

Guideline recommendations are patient-centered. Regardless of setting or the availability of 

professional expertise, any patient in the healthcare system should be provided with the interventions 

that are recommended in this guideline and found to be appropriate to the patient’s specific condition. 

Treatment and care should take into account a patient’s needs and preferences. Good communication 

between healthcare professionals and the patient is essential. It should be supported by evidence-based 

information tailored to the patient’s needs. The information that patients are given about treatment 

and care should be culturally appropriate and available to people who do not speak or read English or 

who have limited literacy skills. It should also be accessible to people with additional needs such as 

physical, sensory or learning disabilities.

Care of Veterans and Service Members in transition between facilities, services, or from the DoD healthcare system to the VHA should have a transition plan and be managed according to best practice 

guidance. Healthcare teams should work collaboratively to provide assessment and services to patients 

within this transitioning population. Management should be reviewed throughout the transition 

process, and there should be clarity about who is the lead clinician to ensure continuity of care.
October 2014 Page 12 of 135

Implementation

This CPG and algorithm are designed to be adapted by individual facilities in consideration of local needs 

and resources. The algorithm serves as a guide that providers can use to determine best interventions 

and timing of care for their patients in order to optimize quality of care and clinical outcomes. 

Although this CPG represents the prevailing practice on the date of its publication, medical practice is 

evolving and this evolution requires continuous updating based on current published information. New 

technology and more research will improve patient care in the future. The CPG can assist in identifying 

priority areas for research and optimal allocation of resources. Future studies examining the results of 

CPGs may lead to the development of new practice-based evidence.
October 2014 Page 13 of 135

Guideline Working Group

Guideline Working Group*

VA DoD

William Cushman, MD

Co-Chair

LCDR Travis Harrell, MD, FACP

Co-Chair 

Dan Berlowitz, MD, MPH James Abbott, MD

Elaine Furmaga, PharmD Angela Allerman, PharmD, BCPS

Sally Peterson, RN Corinne Devlin, MSN, RN, FNP-BC

Lillian Pinault, MS, RD, CDE Maria O’Dowd, RN

Pedro Roldan, MD LCDR Bob Selvester, MD

Gale H. Rutan, MD, MPH, FACP Maj Tracy Snyder MS, RD

Addison A. Taylor, MD, PhD, FAHA LCDR Mark Tschanz, DO

LCDR Jacqueline Vanmoerkerque, DPT

The Office of Quality, Safety and Value

M. Eric Rodgers, PhD, FNP, BC

René M. Sutton, BS, HCA

Clinical Performance Assurance Directorate, 

US Army MEDCOM

Ernest Degenhardt, COL USA (Ret.), MSN, RN, ANP, FNP 

Corinne Devlin, MSN, RN, FNP-BC 

Lewin Group

Cliff Goodman, PhD

Fran Murphy, MD

Hillary Kleiner, MPH

Christine Jones, MS, MPH

Nicolas Stetter, MD, MSCE

*Bolded names are members of the core editing panel. Additional contributor contact information is available in

Appendix F. 
October 2014 Page 14 of 135

Algorithm 
October 2014 Page 15 of 135
October 2014 Page 16 of 135

Recommendations

Recommendation Strength of 

Recommendation

Screening, Diagnosis and Measurement of Hypertension

Screening

1. We recommend screening adults for elevated blood pressure occur periodically,

preferably annually. (Modified from 2004 VA/DoD HTN CPG without an updated

systematic review of the evidence.*)

Strong for

2. We suggest that screening occur at the time of routine preventive care or

routine health assessment. (Modified from 2004 VA/DoD HTN CPG without an

updated systematic review of the evidence.)

Weak for

Diagnosis 

3. We recommend the diagnosis of hypertension be determined based on at least

two blood pressure readings on two separate patient visits. (Modified from 2004

VA/DoD HTN CPG without an updated systematic review of the evidence.)

Strong for

Measurement Techniques

4. We recommend that blood pressure be measured with a technique

recommended for the measurement of blood pressure in adults using a properly

calibrated and validated sphygmomanometer. (Modified from 2004 VA/DoD

HTN CPG without an updated systematic review of the evidence.)

Strong for

5. For patients whose diagnosis of hypertension remains uncertain, we

recommend offering home blood pressure monitoring to confirm diagnosis prior

to beginning pharmacologic treatment. (Two to three times a day for seven

consecutive days, disregard the first day and take the average of

measurements.)

Strong for

6. For patients whose diagnosis of hypertension remains uncertain, we suggest

offering 24 hour ambulatory blood pressure monitoring as an alternative to

home blood pressure monitoring to confirm diagnosis prior to beginning

pharmacologic treatment.

Weak for

Adherence to Therapy

7. We suggest offering a multi-modal approach to adherence interventions, which

could include telemonitoring, multi-disciplinary group medical appointments,

(e.g., shared medical appointments), case management (by pharmacists, nurses,

social workers), patient and provider education, behavioral therapy, etc.

Weak for

Lifestyle Modification

8. We recommend offering lifestyle modification interventions for patients with

prehypertension or hypertension based on patient indications and preferences

as well as assessment of available local resources. (Modified from 2004 VA/DoD

HTN CPG)

Strong for

Weight Reduction

9. We recommend discussing healthy weight range and advising overweight or

obese hypertensive patients to reduce their body mass index to below 25.

(Modified from 2004 VA/DoD HTN CPG)

Strong for
October 2014 Page 17 of 135

Recommendation Strength of 

Recommendation

10. If a normal body mass index (<25) cannot be achieved, we suggest advising

patients that a weight reduction of at least 10 pounds can achieve a decrease in

blood pressure.

Weak for

Exercise/Physical Activity

11. We recommend a target for aerobic exercise of 30 to 45 minutes per session, at

least four times per week. (Modified from 2004 VA/DoD HTN CPG)

Strong for

12. We suggest the use of a self-monitoring device (e.g., pedometer, mobile apps,

etc.) to increase adherence to physical activity.

Weak for

Mind-body Therapies

13. For patients interested in complementary and alternative medicine, we suggest

considering mind-body therapies such as transcendental meditation or yoga.

Weak for

14. We suggest not offering Tai Chi for the treatment of hypertension as there is a

moderate body of evidence that shows this intervention does not reduce blood

pressure.

Weak against

Dietary Modification

15. We recommend a dietitian-led Dietary Approaches to Stop Hypertension (DASH)

Diet for the treatment and/or prevention of hypertension for patients with

hypertension and/or interested patients with prehypertension and other

cardiovascular risk factors. (Modified from 2004 VA/DoD HTN CPG)

Strong for

16. In patients with additional cardiovascular risk factors, such as dyslipidemia, we

suggest considering a dietitian-led Mediterranean Diet as an alternative to the

DASH Diet.

Weak for

17. We recommend against the use of soy protein supplements for the treatment of

hypertension.

Strong against

Sodium Reduction

18. In patients with hypertension or prehypertension, we recommend that sodium

intake be limited to no more than 2300mg/day (100mmol/day), with referral to

a dietitian or other support as appropriate. (Modified from 2004 VA/DoD HTN

CPG)

Strong for

Alcohol Reduction

19. We recommend advising hypertensive and prehypertensive patients to limit

alcohol intake to no more than 1 oz per day for men or 0.5 oz of alcohol per day

for women. (This is approximately 2 drinks/day in men and 1 drink/day in

women, where a drink is 1.5 oz 80-proof liquor, 12 oz beer, or 5 oz wine [all

14g]). (Modified from 2004 VA/DoD HTN CPG)

Strong for

Pharmacological Therapy

Initiation of Pharmacotherapy

20. We recommend offering pharmacologic treatment for hypertensive patients 60

years and older with a systolic blood pressure ≥ 160 mmHg.

Strong for

21. We suggest considering pharmacologic treatment using a shared decision- Weak for
October 2014 Page 18 of 135

Recommendation Strength of 

Recommendation

making model for hypertensive patients 60 years and older with systolic blood 

pressure <160 mmHg. 

22. We suggest offering pharmacologic treatment to patients with a history of

cerebrovascular disease (stroke, transient ischemic attack, or asymptomatic

carotid artery disease) and a systolic blood pressure ≥140 mmHg.

Weak for

23. We suggest pharmacologic treatment for hypertensive patients younger than 60

with a systolic blood pressure ≥160 mmHg, regardless of diastolic blood

pressure.

Weak for

24. We recommend offering pharmacologic treatment for patients 30 years and

older with a diastolic blood pressure ≥90 mmHg.

Strong for

25. We suggest offering pharmacologic treatment for patients age 18 to 29 with a

diastolic blood pressure ≥90 mmHg.

Weak for

Blood Pressure Goals

26. For patients 60 years and over, we recommend treating to a systolic blood

pressure goal of <150 mmHg.

Strong for

27. For patients below 60 years of age, we suggest treating to a systolic blood

pressure goal of <150 mmHg.

Weak for

28. We recommend treating to a diastolic blood pressure goal <90 mmHg in

patients 30 years and older.

Strong for

29. We suggest treating to a diastolic blood pressure goal <90 mmHg in patients age

18 to 29.

Weak for

30. For patients with diabetes (all age groups), we recommend treating to a systolic

blood pressure goal of <150 mmHg.

Strong for

31. For patients with diabetes (all age groups) who tolerate antihypertensive drugs,

we suggest treating to a systolic blood pressure goal of <140 mmHg.

Weak for

32. For patients with diabetes, we recommend treating to a diastolic blood pressure

goal <85 mmHg.

Strong for

Hypertension Control and Follow-up

33. We suggest that patients be seen within one month of initiation of lifestyle or

pharmacological therapy to determine adequacy of hypertension control,

degree of patient adherence, and presence of adverse effects. (Modified from

2004 VA/DoD HTN CPG without an updated systematic review of the evidence.)

Weak for

34. Once the patient’s blood pressure is controlled, we suggest follow-up at least

annually, or more frequently as indicated, depending on patient preference.

(Modified from 2004 VA/DoD HTN CPG without an updated systematic review of

the evidence.)

Weak for

Monotherapy or Combination Therapy

35. We suggest taking into consideration the patient’s baseline blood pressure and

presence of comorbidities, when deciding on either monotherapy or

combination therapy (two drugs) when initiating drug therapy. (Modified from

Weak for
October 2014 Page 19 of 135

Recommendation Strength of 

Recommendation

2004 VA/DoD HTN CPG without an updated systematic review of the evidence.)

36. We suggest initiating combination therapy for patients with a baseline systolic

blood pressure of >20 mmHg or diastolic blood pressure of >10 mmHg above

the patient’s goal. (Modified from 2004 VA/DoD HTN CPG without an updated

systematic review of the evidence.)

Weak for

First-Line Therapy

37. We recommend the use of thiazide-type diuretics for the treatment of

hypertension.

Strong for

38. We suggest the use of thiazide-type diuretics at recommended treatment doses

as first-line therapy for drug treatment of hypertension either as monotherapy

or in combination with other agents. (Modified from 2004 VA/DoD HTN CPG)

Weak for

39. To initiate treatment of hypertension with a thiazide-type diuretic, we suggest

the use of chlorthalidone or indapamide over hydrochlorothiazide.

Weak for

40. We do not suggest switching from hydrochlorothiazide to chlorthalidone or

indapamide if the patient is adequately controlled on and tolerating

hydrochlorothiazide.

Weak against

41. We suggest considering a switch from hydrochlorothiazide to chlorthalidone for

patients whose hypertension is inadequately controlled on 50mg/day of

hydrochlorothiazide.

Weak for

42. We recommend a dosage of 12.5-25mg/day of chlorthalidone, 25-50mg/day of

hydrochlorothiazide, or a dosage of 2.5mg/day immediate-release or 1.5-

2.5mg/day sustained-release (not currently available in the US) of indapamide.

Strong for

Alternative or Supplementary Therapies

43. We recommend using the following as alternative therapies for patients who

cannot tolerate thiazide-type diuretics, as supplementary therapies for patients

who do not reach their hypertensive goals, or for those starting on combination

therapy:

a. Angiotensin-converting-enzyme inhibitors or angiotensin II receptor

blockers (but not together)

b. Long-acting dihydropyridine calcium channel blockers

(Modified from 2004 VA/DoD HTN CPG)

Strong for

44. We recommend against the use of more than one of the following three drug

classes together in the same patient: angiotensin-converting-enzyme inhibitors,

angiotensin II receptor blockers, or direct renin inhibitors.

Strong against

45. We recommend additional therapy in refractory hypertension (for those who do

not tolerate or are not adequately controlled with triple therapy [i.e., thiazidetype diuretics, ACEI or ARB, and CCBs] described in Recommendation 43) or as

supplementary therapy in some clinical indications. Drug classes for

consideration can include (not in priority order):

a. Aldosterone/mineralocorticoid receptor antagonists (e.g.,

spironolactone, eplerenone)

Strong for
October 2014 Page 20 of 135

Recommendation Strength of 

Recommendation

b. Other potassium-sparing diuretic (i.e., amiloride)

c. Alpha adrenergic blockers

d. Beta adrenergic blockers

e. Non-dihydropyridine calcium channel blockers

f. Combined alpha-beta adrenergic blockers

g. Peripherally acting antiadrenergic agents (reserpine, pending

availability)

h. Direct acting vasodilators (e.g., hydralazine, minoxidil)

i. Centrally acting antiadrenergic drugs (e.g., clonidine, methyldopa)

46. We recommend against the use of alpha-adrenergic blockers as monotherapy,

but this class of agents may be used as supplemental therapy or if warranted by

comorbid conditions (e.g., symptomatic prostatic hypertrophy). (Modified from

2004 VA/DoD HTN CPG)

Strong against

Specific Populations

47. In patients with hypertension and chronic kidney disease (reduced kidney

function with albuminuria), we recommend treatment with an angiotensinconverting-enzyme inhibitor, or angiotensin II receptor blocker for improving

kidney outcomes. (Modified from 2004 VA/DoD HTN CPG)

Strong for

48. In African American patients with hypertension, we recommend against using an

angiotensin-converting-enzyme inhibitor or angiotensin II receptor blocker as

monotherapy.

Strong against

49. In African American patients with hypertension and stage 1-3 chronic kidney

disease, we suggest a combination of a thiazide-type diuretic (for cardiovascular

protection) with either an angiotensin-converting-enzyme inhibitor or

angiotensin II receptor blocker (for renal protection).

Weak for

* For additional information please refer to Reconciling 2004 CPG Recommendations.
October 2014 Page 21 of 135

Screening, Diagnosis and Measurement of Hypertension

Screening

Recommendations 

1. We recommend screening adults for elevated blood pressure occur periodically, preferably

annually. (Modified from 2004 VA/DoD HTN CPG without an updated systematic review of the

evidence.)

2. We suggest that screening occur at the time of routine preventive care or routine health

assessment. (Modified from 2004 VA/DoD HTN CPG without an updated systematic review of the

evidence.)

Discussion

A 2007 updated review of the evidence for the USPSTF describes the rationale for blood pressure 

screening. [14] Based on their review, the USPSTF concludes that the benefits of blood pressure 

screening far outweigh any risks. The risk for cardiovascular events and the potential benefit from 

screening and subsequent treatment of hypertension depend on both the degree and duration of blood 

pressure elevation and the presence of other cardiovascular risk factors, such as age, gender, lipid 

disorders, smoking, and diabetes. Because the degree and duration of blood pressure elevation are 

unknown before screening, selective screening to identify individuals who would benefit most from 

detection and treatment of hypertension would need to target individuals with other cardiovascular risk 

factors. No studies were found that examined the relative effectiveness, cost-effectiveness, or harms of 

targeting screening for hypertension only to those patients with other cardiovascular risk factors instead 

of to all patients who present at a physician’s office. Additionally, no studies were found that examined 

the optimal frequency of screening based on a patient’s prior blood pressure levels or other 

cardiovascular risk factors.

For patients who are screened, estimates of the potential benefit of treatment can be improved both by 

carefully measuring the degree of blood pressure elevation and by assessing the contribution of other 

risk factors to global cardiovascular risk. [15-17] 

Since increasing age is related to greater incidence of hypertension, and because lifetime risk is so high 

(approximating 90% for octogenarians), it is sensible to screen periodically. The risk of proceeding to 

hypertension is summarized in Table 1, which was adapted from Vasan et al. (2001). [18] 

Table 1. Incidence Rates of Hypertension at 1, 2 and 3 Years

Baseline Blood Pressure (BP) Category† Age 35-64 Years Age 65-94 Years

% hypertension at 1 year (95 CI)*

Optimum BP 1.3 (1.1-1.6) 4.3 (3.1-5.7)

Normal BP 4.7 (4.0-5.5) 7.1 (5.5-9.0)

High Normal BP 11.0 (9.6-12.6) 15.7 (13.0-18.8)

% hypertension at 2 year (95 CI)*

Optimum BP 2.7 (2.2-3.2) 8.3 (6.2-11.1)

Normal BP 9.2 (7.9-10.7) 13.7 (10.8-17.2)

High Normal BP 20.8 (18.3-23.5) 28.9 (24.2-34.0)
October 2014 Page 22 of 135

Baseline Blood Pressure (BP) Category† Age 35-64 Years Age 65-94 Years

% hypertension at 3 year (95 CI)*

Optimum BP 4.0 (3.3-4.8) 12.2 (9.2-16.1)

Normal BP 13.5 (11.6-15.7) 19.8 (15.7-24.6)

High Normal BP 29.6 (26.2-33.1) 40.1 (34.0-46.4)

*Rates are per 100, and are adjusted for sex, age, body mass index, baseline examinations,

and baseline systolic and diastolic BP.

† Optimal BP: <120/80 mmHg; Normal BP: SBP 120-129 mmHg and DBP= 80-84 mmHg; High 

Normal: SBP= 130-139 mmHg and DBP= 85-89 mmHg

The optimal screening intervals have not been determined in clinical studies; however, as most patients 

over 50 years old routinely seek care at least annually for medical conditions and/or other preventive 

care (e.g., immunizations and screening for colorectal cancer, breast cancer, skin cancer, osteoporosis, 

and/or diabetes), it is clinically appropriate to also screen for hypertension at that time. In addition, 

consideration should be given to annual screening for those patients of any age who have other

cardiovascular risk factors. Younger patients without risk factors have a lower incidence of hypertension 

in the short term, but, if possible, annual screening–which is relatively easy to perform when patients 

attend clinics for preventive care or routine health assessments–should be considered. 

Diagnosis

Recommendation

3. We recommend the diagnosis of hypertension be determined based on at least two blood

pressure readings on two separate patient visits. (Modified from 2004 VA/DoD HTN CPG without

an updated systematic review of the evidence.)

Discussion

The definition of hypertension is somewhat arbitrary because the relationship between systemic arterial 

pressure and morbidity appears to be linear from 115/75 mmHg, [19] but the evidence supporting 

benefit from treatment of elevated blood pressure starts at a higher threshold. Table 2 below reflects 

thresholds for establishing the diagnosis of hypertension, which remains independent of treatment 

thresholds and intervention decisions. Further complicating this diagnosis, the defined limits for optimal

blood pressure vary based on time of day and method of measurement. Table 2 is useful to facilitate the 

diagnosis of hypertension in adults aged 18 years or older based on office blood pressure readings.

Treatment decisions based on the diagnostic criteria listed in the table are discussed extensively below, 

and are determined by age and comorbid conditions.

Table 2. Follow-Up Based on Initial Classification of Blood Pressure for Adults 

SBP (mmHg) DBP (mmHg) Follow-up

Optimal

< 120 < 80 Recheck in two years

Prehypertension

120-139 80-89 Recheck in one year
October 2014 Page 23 of 135

SBP (mmHg) DBP (mmHg) Follow-up

Hypertension

> 140 > 90 Confirm within 1-4 weeks

Due to significant variability in office readings, we suggest that the diagnosis of hypertension should be 

made after at least two elevated measurements per visit on multiple visits one to four weeks apart. 

Typically, the blood pressure will decrease with subsequent readings. This suggestion is supported by 

the evidence review for the Eighth Joint National Committee (JNC8) as well as the evidence review for 

the USPSTF recommendations. [20] Special attention must be paid to proper measurement of blood 

pressure, as improper equipment or technique may lead to misdiagnosis (see Recommendation 4). 

Measurements are only accurate for diagnosis of hypertension when the patient is not acutely ill or 

injured.

Prehypertension is not a disease category, but a classification to signify an increased risk for progression 

to hypertension. Patients in the upper range of prehypertension, with a systolic blood pressure of 130–

139 mmHg or a diastolic blood pressure of 85–89 mmHg are at twice the risk to develop hypertension

compared to the normotensive population. In addition, observational data suggests the risk of 

cardiovascular events and mortality doubles with each 20 mmHg increase in SBP and 10 mmHg increase 

in DBP beginning with a BP of 115/75 mmHg. The designation of prehypertension can alert both the 

patient and provider to increased cardiovascular risk and mortality, and open a discussion on risk 

reduction options.

Medical history and physical examination

The patient’s medical history pertinent to hypertension should include:

1. Duration, levels, and nature of BP elevation

2. History or symptoms of coronary heart disease (CHD), heart failure (HF), cerebrovascular

disease, peripheral vascular disease, renal disease, obstructive sleep apnea, diabetes mellitus

(DM), dyslipidemia, and gout

3. Screening for baseline symptoms of sexual dysfunction, depression, cough, and angioedema

4. Family history of hypertension, premature CHD, cerebrovascular accident (CVA), DM,

dyslipidemia, or renal disease

5. Other symptoms suggesting other causes of elevated BP

6. Results and adverse effects of any previous antihypertensive therapy

7. History of recent change in weight, physical activity, tobacco use

8. Dietary habits, including intake of sodium and total caloric intake

9. History of all prescribed and over-the-counter medications, herbal remedies, and dietary

supplements, some of which may raise blood pressure or interfere with the effectiveness of

antihypertensive medications

10. History of alcohol and illicit drug use (especially cocaine and other stimulants)

11. Psychosocial and environmental factors (e.g., family situation, employment status and working

conditions, level of comprehension) that may influence hypertension control
October 2014 Page 24 of 135

A physical exam should include an evaluation for signs of secondary hypertension or hypertensive organ 

damage. At a minimum, vital signs should include height, weight, and two or more blood pressure 

readings to include one in each arm, with the patient seated. All hypertensive patients should have a 

thorough history and physical examination, but need only a limited number of routine investigations. It 

is beyond the scope of these guidelines to discuss every detail of the clinical evaluation, but it may be 

useful to summarize the aims, which are to elicit and document:

• Causes of secondary hypertension (e.g., renal disease, endocrine causes)

• Contributory factors for primary hypertension (e.g., obesity, excess sodium intake, excess

alcohol intake)

• Complications of hypertension (e.g., previous stroke, LVH, ischemic heart disease [IHD], CKD, HF)

• Cardiovascular risk factors (e.g., smoking, family history)

• Relative or absolute contraindications to specific drugs (e.g., asthma [beta-blockers],

angioedema [ACEIs])

Presence of any target organ damage, associated clinical condition, or history or evidence of a previous 

cardiovascular event substantially increases the risk of subsequent events in hypertensive patients (see 

Table 3). 

Table 3. Initial Evaluation of the Hypertensive Patient

Most common causes of secondary hypertension [21]

• Renal

o Renal artery stenosis

o Polycystic kidney disease

o Chronic reflux nephropathy

o Chronic glomerulonephritis

o Polyarteritis nodosa

o Systemic sclerosis

• Endocrine

o Cushing's syndrome

o Conn's syndrome

o Pheochromocytoma

o Acromegaly

o Hyperparathyroidism

o Polycystic ovarian syndrome

• Other

o Obstructive sleep apnea

o Aortic coarctation

o Pre-eclampsia

o Drugs (combined oral contraceptive pill, cyclosporin, steroids)

o Central nervous system disturbances (raised intracranial pressure, familial

dysautonomia)

Contributory factors to primary hypertension

• Overweight or obesity

• Excess alcohol intake (>2 drinks/day for men, >1 drink/day for women)

• Excess sodium intake

• Low potassium intake

• Lack of physical activity
October 2014 Page 25 of 135

Complications of hypertension/target organ damage

• Stroke, transient ischemic attack (TIA), dementia

• Left ventricular hypertrophy (LVH), heart failure

• Myocardial infarct, angina, coronary artery bypass graft (CABG) or angioplasty

• Peripheral vascular disease

• Fundal hemorrhages or exudates

• Proteinuria

• Renal impairment

Associated clinical conditions [22]

• Diabetes

• Cerebrovascular disease

o Ischemic stroke

o Cerebral hemorrhage

o Transient ischemic attack

• Heart disease

o Myocardial infarction

o Angina

o Coronary revascularization

o Chronic heart failure

• Chronic kidney disease

o Diabetic nephropathy

o Glomerulonephritis

o Hypertensive renovascular disease

• Aortic disease

o Dissecting aneurysm

o Fusiform aortic aneurysm

• Peripheral arterial disease

Routine laboratory tests

Routine tests for all patients at the time of diagnosis of hypertension may include such tests as:

• Urinalysis (UA); if the UA is positive for protein consider a quantitative measure of an albumin to

creatinine ratio

• Blood chemistry (potassium, sodium, blood urea nitrogen [BUN], creatinine, glucose, non-fasting

lipid profiles)

• Twelve-lead electrocardiography (ECG)

Urinalysis is useful in the detection of overt proteinuria. Blood chemistry may be helpful in identifying 

underlying kidney disease, diabetes, and baseline electrolyte abnormalities. Non-fasting lipid profiles 

may assist in global risk factor modification. Twelve-lead ECGs are recommended to assist in the 

identification of LVH or ischemic heart disease. Other tests may be indicated depending upon presence 

of other risk factors and current comorbid conditions (e.g., uric acid for known gout).
October 2014 Page 26 of 135

Measurement Techniques

Recommendations

4. We recommend that blood pressure be measured with a technique recommended for the

measurement of blood pressure in adults using a properly calibrated and validated

sphygmomanometer. (Modified from 2004 VA/DoD HTN CPG without an updated systematic

review of the evidence.)

5. For patients whose diagnosis of hypertension remains uncertain, we recommend offering

home blood pressure monitoring to confirm diagnosis prior to beginning pharmacologic

treatment. (Two to three times a day for seven consecutive days, disregard the first day and

take the average of measurement.)

6. For patients whose diagnosis of hypertension remains uncertain, we suggest offering 24 hour

ambulatory blood pressure monitoring as an alternative to home blood pressure monitoring to

confirm diagnosis prior to beginning pharmacologic treatment.

Discussion

The diagnosis of hypertension has been traditionally based on measurement of blood pressure in a 

medical clinic or office. A minimum of two measurements made at least one minute apart are averaged,

according to American Heart Association (AHA) guidelines. These same criteria were used in outcomes 

trials demonstrating the benefit of antihypertensive therapy. [23] A confounding variable in these 

measurements is the phenomenon of the alerting reaction or “white coat effect” which is exhibited by 

most patients. The initial one to two blood pressures are typically higher than subsequent BP readings 

and the extent of this “white coat effect” varies widely among patients. Studies evaluating this 

phenomenon have documented higher readings when blood pressure is taken by physicians than when 

taken by a nurse or medical assistant. To obtain the values most representative of the patient’s office 

blood pressure, it is recommended that at least two readings be taken on each of two occasions, at least 

one day apart. The AHA recommendations for blood pressure measurement include the following key 

points: [24] 

• Patient should be seated quietly for five minutes with back supported, feet on the floor, and

arm bared, unrestricted by clothing, and supported at heart level. Measurement of BP in the

standing position may be indicated for patients at risk for postural hypotension or at the

discretion of the clinician. Standing BP should be measured with the bared arm supported at

heart level.

• Smoking, exercise, or caffeine ingestion should not have occurred within 30 minutes prior to the

BP measurement.

• The urinary bladder should be emptied before the BP measurement.

• The appropriate blood pressure cuff size should be chosen for the patient (see Table 4). The cuff

should be wrapped snugly around the arm with the bladder centered over the brachial artery.

The bladder should encircle at least 80% of the arm and should not overlap.
October 2014 Page 27 of 135

Table 4. Appropriate Cuff Size Based on Patient’s Arm Circumference [23,24] 

Arm circumference 

(cm)

Cuff size

22-26 Small adult

27-34 Adult

35-44 Large adult

45-52 Very large adult

• If the patient is talking, laughing, sneezing or coughing during the BP measurement (activities

that affect blood pressure), the reading should be discarded and the measurement repeated.

• On the initial clinic visit, blood pressure should be measured in both arms. If there is a

consistently large (>10-15 mmHg) difference between arms, the arm with the higher blood

pressure readings should be used routinely as the patient’s blood pressure.

For Auscultatory Measurements Only:

• Palpated radial pulse obliteration pressure should be used to estimate the SBP. The cuff should

then be inflated 20-30 mmHg above this level for the auscultatory determinations.

• Position the stethoscope over the brachial artery and rapidly inflate the cuff. Deflate the cuff at

a rate of 2 to 3 mmHg per second, listening for Phase 1 and Phase 5 Korotkoff sounds. The first

appearance of sound (Phase 1) is used to record the SBP. Phase 5, at the disappearance of

sound, is the diastolic blood pressure (DBP). Listen for 10 to 20 mmHg below Phase 5 for any

further sound then deflate the cuff completely.

• The BP should be recorded in even numbers to the nearest 2 mmHg with the patient's position,

arm used, and cuff size documented.

• BP readings should be repeated in the same arm and averaged, if different. One-two minutes

should elapse before repeating the BP measurement. If the readings differ by more than

5mmHg, additional measurements should be obtained.

The recommendations for blood pressure measurements follow the methods used in the many 

randomized trials that have established the benefits of antihypertensive therapy (e.g., Systolic 

Hypertension in the Elderly Program [SHEP], Antihypertensive and Lipid-Lowering Treatment to Prevent 

Heart Attack Trial [ALLHAT]). Using these methods allows the provider to accurately risk stratify patients, 

since epidemiological studies (e.g., Framingham) also used the same measurement techniques.

Blood pressure in the office is most commonly measured with a sphygmomanometer of either the 

ascultatory or oscillometric type. Due to variability in individual blood pressure measurements 

(occurring as a result of instrument, observer, and patient factors), it is recommended that hypertension 

be diagnosed only after two or more elevated readings are obtained on at least two visits over a period 

of one to four weeks, unless there is evidence of hypertension target organ damage.

Office blood pressure measurement is the standard screening test for hypertension. When performed 

correctly, sphygmomanometers provide a measure of blood pressure that is correlated with intraarterial measurement and predictive of cardiovascular risk. [25] However, office blood pressure 
October 2014 Page 28 of 135

measurements can in some cases exhibit significant variability and may not represent the patient’s usual 

blood pressure outside the office setting.

Over the past two decades a proliferation of manual and automated home blood pressure monitoring 

(HBPM) devices and more widespread use of ambulatory blood pressure monitoring (ABPM) has 

allowed comparisons of clinic/office blood pressures with those measured outside the clinic/office, 

either at home (HBPM) or periodically throughout the entire 24 hour day (ABPM). For patients who 

exhibit persistently elevated office blood pressures, confirmatory out of office blood pressure 

measurements should be considered. Home blood pressure devices are usually more readily available 

than ambulatory blood pressure devices, but ABPM results can be utilized when office BP is high and 

home BP is not elevated.

Home blood pressure 

Monitoring of blood pressure at home may selectively assist in diagnosing and managing hypertension. 

Recent studies indicate that self-monitoring may help in differentiating white-coat hypertension (i.e. 

persistently elevated office BP with normotensive BP by home or ambulatory BP readings) from 

chronically high blood pressure readings and/or may provide additional readings in patients who are 

already being treated for hypertension but who also have a white-coat component. [26-28] There is 

some evidence to suggest that home blood pressure monitoring has good prognostic efficacy for 

predicting cardiovascular events. [27,29,30] Home blood pressure monitoring may also identify patients 

who have a normal blood pressure in the office but not at home (so-called “masked” hypertension). [27] 

Several studies have examined the number of measurements, the times of the day and the number of 

days over which the measurements should be made to define the optimal home blood pressure (HBP). 

Collectively, the results of several of these studies suggest that the optimal number of home 

measurements is 12 to 14. [31] A commonly utilized protocol involves measuring blood pressure twice 

daily, morning and evening, for seven days. Measurements are usually made with an automated 

oscillatory device with the subject seated utilizing AHA guidelines for blood pressure measurement. 

Often the blood pressures measured on the first day are discarded since they tend to exhibit the 

greatest variability. In order to improve accuracy and interpretation of home blood pressure 

measurements, the use of a device with a memory function is recommended rather than relying on the 

patient’s recall or diary, though these types of devices may not always be available. From a practical 

standpoint, it may be helpful for patients to bring in their self-monitoring device to the clinic in order to 

calibrate it against an office manometer.

Based on the results of several observational studies, [29,30,32] other guidelines recommend HBP 

criteria for the diagnosis of hypertension to be >135/85 mmHg, as opposed to >140/90 mmHg for clinic

BP criteria. [33] Collectively, the results of these observational studies underscore the value of HBP for 

predicting fatal and nonfatal cardiovascular events, and changes in surrogate cardiac and renal markers 

of cardiovascular injury. However, outcome trials reviewed did not use out of office BPs as either entry 

criteria or as treatment goals, nor have there been randomized trials comparing outcomes when using 

office versus out of office BPs as treatment goals. Therefore, it is not clear if using out of office BPs to 

manage hypertension would improve patient outcomes.
October 2014 Page 29 of 135

Ambulatory blood pressure

If there is a significant discrepancy between HBPM and clinic blood pressure (CBP), ABPM can be 

considered as an alternate for confirming the diagnosis of hypertension in a patient with persistently 

elevated office blood pressure. The ABPM device includes a cuff affixed to the patient’s arm, connector 

tubing and a combination inflator, programmable recorder, and battery pack with a strap which can be 

secured to the waist or worn over the shoulder. The device is most commonly programmed to obtain 

readings every 15-20 minutes during the day and every 30 minutes at night. After 24 hours of data 

collection, the memory is downloaded to a computer for analysis. ABPM is currently the primary way to 

capture information about blood pressure when the patient is sleeping. 

Like HBP, ambulatory blood pressure has been reported to be a stronger predictor of cardiovascular 

events and of target organ damage than CBP in observational studies. [34,35] However, it should be 

reiterated that there are no outcome trials that have used out of office BPs as either entry criteria or as 

treatment goals, nor have there been randomized trials comparing outcomes when using office versus 

out of office BPs as treatment goals. Therefore, it is not clear if using out of office BPs to manage 

hypertension would improve patient outcomes. 

While we did not identify head-to-head comparison studies between home and ambulatory blood 

pressure, both approaches seem to improve the predictive value of office blood pressure to a similar 

extent and seem to be of similar value to help make a decision for medication initiation. As home blood 

pressure is more readily available to patients and require fewer resources, we recommend offering 

home blood pressure for most patients whose diagnosis of hypertension remains uncertain. 

Adherence to Therapy

Recommendation

7. We suggest offering a multi-modal approach to adherence interventions, which could include

telemonitoring, multi-disciplinary group medical appointments, (e.g., shared medical

appointments), case management (by pharmacists, nurses, social workers), patient and

provider education, behavioral therapy, etc.

Discussion 

Inadequate blood pressure control may be attributed to patients not adequately adhering to the 

medication regimen [36] and successful treatment for hypertension has been related to adherence. [37-

40] It has been reported inadequate adherence to prescribed medications is found in the majority of

cases of uncontrolled hypertension. [41,42] 

Numerous causes of poor medication adherence have been suggested, including long-term therapy, 

cognitive impairment, number of medications prescribed, frequency of administration, complexity of 

the drug regimen, cost of medications, side effects, and factors related to the patient’s health decisions 

(e.g., acceptance of the disease, perceived severity, satisfaction with healthcare interaction, etc.). [42] 

Other factors may include patient and/or caregiver education on the disease and its management, 
October 2014 Page 30 of 135

healthcare practitioner patient communication skills, the extent to which the patient is involved in selfmanagement of HTN, and monitoring by the healthcare professional. [43] 

Several approaches to improving adherence to hypertension treatment regimens have been studied. In 

general, multi-modal approaches to improving adherence have been the most effective. Approaches 

which focused only on provider or patient education [44-48] or a self-monitoring device [49] outside of a 

structured supervision program were not successful in decreasing blood pressure or increasing the 

percentage of patients with controlled hypertension. 

The Hypertension Intervention Nurse Telemedicine Study (HINTS) was a Department of Veterans Affairs 

based study which found that combining nurse administered behavioral management and medication 

management interventions demonstrated sustained improvements in blood pressure. [50-52] 

Group medical clinics (GMCs) at two Veterans Affairs Medical Centers (VAMCs), which consisted of a 

primary care general internist, a pharmacist, and a nurse or other certified diabetes educator, were also 

shown to improve blood pressure control compared to usual care. [53] 

Multiple studies have focused on improvements in adherence to antihypertensive medications and its 

effect on the control of hypertension through the use of nurse- or pharmacist-directed case 

management. These have used a variety of techniques, including telemonitoring, [54] electronic-web 

based monitoring and communication, [55] and structured in-person or telephone-based follow-up for 

medication management. [56-59] Each of these strategies improved the adherence to medications, 

decreased blood pressure, and improved the percent of patients with adequate control of hypertension. 

In addition, the study by Dennison et al. demonstrated a reduction in the percent of patients who 

developed left ventricular hypertrophy after five years. [56] These interventions were performed in 

different populations and different clinical settings. The common feature for them was a focus on 

structured follow-up and monitoring for the patients.

Two studies utilized an electronic health record-based clinical decision support system which suggested 

specific changes in medications for patients not meeting individualized blood pressure goals. However, 

they did not demonstrate a significant difference in change in systolic blood pressure and diastolic blood 

pressure compared to usual care. [60,61] 

Many of the multi-modal or nurse/pharmacist-directed case management models are successful but can 

be resource intensive. However, it is important to understand the baseline rates of hypertension 

control, medical adherence, cultural barriers, and local resources prior to implementing a specific 

intervention. Additionally, the effects of these programs tend to decrease over time or when the 

frequency of monitoring is decreased. Therefore, patients should be monitored for a decrease in control 

or enrolled into a chronic disease management program to help maintain control. For patients with a 

decrease in control of hypertension, providers should consider enrolling them back into a more 

intensive program. 

Further research should focus on how to identify the aspects of a system or population which will 

predict the adherence intervention modality which is most likely to improve adherence to 
October 2014 Page 31 of 135

pharmacologic and lifestyle modification therapy and control of hypertension. Currently, it appears that 

patients who have high baseline blood pressure values or poor baseline control rates derive the greatest 

benefit from these intervention programs. 

Lifestyle Modification Therapies

Recommendation

8. We recommend offering lifestyle modification interventions for patients with prehypertension

or hypertension based on patient indications and preferences as well as assessment of

available local resources. (Modified from 2004 VA/DoD HTN CPG)

Discussion

Lifestyle modification should be prescribed by clinicians for patients whose blood pressure is in the 

prehypertension or hypertension range. Lifestyle modification strategies which have been demonstrated 

to lower blood pressure include: weight reduction for patients who are overweight or obese, increased 

physical activity, mind-body therapies, change in dietary pattern, sodium reduction, and moderation of 

alcohol intake. These interventions can be combined with each other and with pharmacologic 

treatments to lower blood pressure as well. Some of these lifestyle modifications have health benefits 

beyond their blood pressure lowering effects, such as reduced risk for diabetes, improved lipid profile, 

and decreased risk for cardiovascular and liver disease.

Weight Reduction

Recommendation

9. We recommend discussing healthy weight range and advising overweight or obese

hypertensive patients to reduce their body mass index to below 25. (Modified from 2004

VA/DoD HTN CPG)

10. If a normal body mass index (<25) cannot be achieved, we suggest advising patients that a

weight reduction of at least 10 pounds can achieve a decrease in blood pressure.

Discussion

Overweight and obesity represent a significant burden to the DoD and VA healthcare systems, with 

national surveys estimating that 60.5% [62] of active duty military personnel and 71.5% [63] of Veterans 

are overweight or obese. Excess body weight has been linked directly to multiple disease processes, 

including hypertension. Weight loss as part of a comprehensive lifestyle management program has been 

shown to reduce blood pressure in individuals with or without hypertension.

Multiple studies have examined the impact of weight loss on cardiovascular risk factors. The Look 

AHEAD (Action for Health in Diabetes) trial evaluated the long-term impact of intensive lifestyle 

interventions (ILI) on cardiovascular morbidity and mortality in overweight or obese individuals with 

type 2 diabetes. [64] The study examined the impact of an ILI, which included dietary modification and 

physical activity, compared with usual care and examined the changes in weight, fitness, glycemic 

control and cardiovascular disease risk factors. At the end of four years, individuals in the ILI group 
October 2014 Page 32 of 135

averaged a 6.15% weight loss compared to a 0.88% loss in the control group. Both groups experienced 

reductions in SBP and DBP; however, reductions were only statistically significant for the ILI group. 

While 80% of the subjects had a history of hypertension, the mean blood pressure at baseline was only 

128-129/70 mmHg. 

From February 1999 to February 2002, Esposito et al. examined the impact of weight loss and lifestyle 

on inflammatory markers in healthy, obese women. [65] One hundred twenty premenopausal obese 

women were assigned to either the lifestyle intervention group, which received detailed counseling on a 

10% weight reduction, or the control group, which was only given written information on healthy food 

choices and exercise. After two years, both groups showed significant weight loss; however, women in 

the intervention group lost significantly more body weight than those in the control group. Both groups 

also showed significant decreases in blood pressure with a larger effect in the intervention group. [65] 

Gardner et al. compared the effects of four weight-loss diets representing a spectrum of high to low 

carbohydrate recommendations on weight loss and related metabolic variables over 12 months in 311 

normotensive premenopausal women with a BMI of 27 to 40. [66] Participants were randomly assigned 

to follow the Atkins, Zone, Lifestyle Exercise Attitudes Relationships Nutrition [LEARN], or Ornish diets 

and received weekly instruction for two months and then were followed-up for an additional ten 

months without further instruction. At study end, the percentage of weight lost in women assigned to 

the Atkins diet was greater compared to all other groups (Atkins -2.9%, Zone -1.3 %, LEARN -1.0%, 

Ornish -1.5%). All groups showed reductions in SBP and DBP from baseline; however, the Atkins group 

showed significantly greater average reduction in SBP compared to all other groups. Although only 

significantly different than the Ornish group, the Atkins group also demonstrated greater reductions in 

DBP. [66] 

A systematic review of several randomized controlled trials (RCTs) by Aucott et al. [67] examined the 

long-term effect of weight loss on hypertension outcome measures after two years. The findings of this 

review suggested that a 5 kg weight loss may be correlated with an average reduction in SBP of 5.6 

mmHg. Similarly, a meta-analysis of 25 shorter term studies [68] suggested decreases of 1.05 mmHg and 

0.92 mmHg for SBP and DBP, respectively, when expressed per kilogram of weight loss.

Exercise/Physical Activity

Recommendation

11. We recommend a target for aerobic exercise of 30 to 45 minutes per session, at least four

times per week. (Modified from 2004 VA/DoD HTN CPG)

12. We suggest the use of a self-monitoring device (e.g., pedometer, mobile apps, etc.) to increase

adherence to physical activity.

Discussion

The target for aerobic exercise should be 30 to 45 minutes per session, [69-71] at least four per week to 

reduce blood pressure, which is consistent with the 2008 Physical Activity Guidelines for Americans, 

which address the prevention of a larger range of health conditions. [72] Although evidence for 

resistance training is limited, there is no basis to exclude resistance training from a program of exercise, 
October 2014 Page 33 of 135

and it may confer benefits in patients. The use of self-monitoring adherence devices is recommended 

for maximum benefits from physical activity. Self-monitoring devices, such as pedometers, have been 

shown to improve adherence to exercise regimens, causing greater reductions in blood pressure when 

compared to patient education or prescriptions for exercise alone. [73,74] Structured and supervised 

exercise programs provide greater blood pressure reduction when compared to usual care or 

counseling. [75,76] 

Mind-body Therapies 

Recommendations 

13. For patients interested in complementary and alternative medicine, we suggest considering

mind-body therapies such as transcendental meditation or yoga.

14. We suggest not offering Tai Chi for the treatment of hypertension as there is a moderate body

of evidence that shows this intervention does not reduce blood pressure.

Discussion

Limited studies on transcendental meditation suggest that this technique may decrease the progression 

of hypertension when practiced regularly. [77,78] Yoga, when performed regularly for 35-40 minutes 

per day, five days per week, may provide a reduction in blood pressure. [79] Tai Chi, another form of 

mind-body therapy, has not been proven to be an effective form of alternative therapy in the reduction 

of blood pressure. [80] 

Dietary Modification

Recommendations 

15. We recommend a dietitian-led Dietary Approaches to Stop Hypertension (DASH) Diet for the

treatment and/or prevention of hypertension for patients with hypertension and/or interested

patients with prehypertension and other cardiovascular risk factors. (Modified from 2004

VA/DoD HTN CPG)

16. In patients with additional cardiovascular risk factors, such as dyslipidemia, we suggest

considering a dietitian-led Mediterranean Diet as an alternative to the DASH Diet.

17. We recommend against the use of soy protein supplements for the treatment of hypertension.

Discussion 

Clinical trials on supplements frequently produce different or even opposite results than those expected 

based on epidemiologic data showing associations between food constituents and health outcomes. As 

we consume whole foods rather than isolated nutrients, it is more useful to confirm that a pattern of 

whole foods confers benefit, rather than that a micro/macronutrient is beneficial dependent on context. 

Fiber and various micronutrients such as potassium, magnesium and calcium are thought to improve

blood pressure based on epidemiologic data. The DASH diet represents the first major clinical trial to 

test a dietary pattern for the prevention and/or management of hypertension, and emphasized 

inclusion of these nutrients via commonly consumed foods, rather than supplements. [81] This approach 

allows for the detection of potential additive and/or synergistic effects of these nutrients which might 
October 2014 Page 34 of 135

individually be too small to detect. The DASH diet has been shown to reduce SBP and DBP in both 

hypertensive and normotensive adults, whether at dietary sodium intakes similar to the average daily 

consumption [82] or in combination with varying degrees of sodium reduction. [83] Combining the DASH 

diet with sodium reduction consistently produces larger decreases in blood pressure than either 

intervention alone across diverse subgroups. [84] No new evidence met criteria for review during this 

CPG update; the current guideline continues to recommend the DASH diet based on the existing body of 

evidence to support its use in lowering blood pressure. 

Epidemiologic data has also long suggested a cardio-protective effect of a Mediterranean style diet.

Despite known variation in the cuisine of Mediterranean countries, certain characteristic features are 

commonly used to describe a traditional Mediterranean diet: high intake of vegetables, fruits, nuts, 

unrefined grains and olive oil; moderate intake of fish and poultry; low or moderate intake of wine; and 

low intake of red meat, processed meat, dairy and sweets. Toledo et al. [85] evaluated the effects of a 

Mediterranean diet on blood pressure in the PREDIMED (PREvención con DIeta MEDiterránea) trial in 

Spain, a large cohort of men and women at high cardiovascular risk. The two intervention groups 

received individual and group education on an energy-unrestricted Mediterranean diet from registered 

dietitians, as well as regular supplies of either extra-virgin olive oil or mixed nuts. The control group 

received a similar format of education on a low-fat diet. Statistically significant improvements in DBP, 

but not SBP, were found for both intervention groups when compared to controls at four years. [85] 

Furthermore, the two groups randomized to the Mediterranean diet experienced a significant 28-30% 

reduction in major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular 

causes). [86] 

Additional research is needed to test the Mediterranean diet in RCTs of more diverse populations, and 

against controls with more dissimilar baseline and intervention dietary patterns. In the meantime, a 

Mediterranean-style dietary pattern may be beneficial to patients with hypertension, and presents a 

viable alternative to the DASH diet for patients who find lower fat diets unpalatable or otherwise prefer 

the Mediterranean dietary pattern. For either dietary pattern, patients should be offered referral to a 

registered dietitian to help achieve the desired changes. 

Additional dietary information on both the DASH and Mediterranean diets can be found in Appendix C. 

Howard et al. reported cardiovascular outcomes from the Women's Health Initiative Dietary 

Modification Trial. [87] This RCT tested an intensive behavioral modification intervention in a large, freeliving cohort of postmenopausal women, and found that a low-fat diet did not reduce blood pressure, 

stroke or myocardial infarction at a mean follow-up of 8.1 years. While a low-fat diet may be desirable 

for other medical conditions, targeting fat content alone is not recommended as a sole dietary strategy 

for the treatment of hypertension specifically.

Epidemiologic data on soy and isoflavone intake in Asian countries suggests that phytoestrogen 

consumption may mitigate the increased cardiovascular disease incidence seen in postmenopausal 

women. However, an RCT from the Netherlands compared the effects of supplemental soy protein 

(containing 99mg isoflavones) to milk protein on vascular function in postmenopausal women. [88] After 
October 2014 Page 35 of 135

12 months, SBP increased significantly more in the soy protein group when compared with the control 

group; a non-statistically significant increase in DBP was also noted for the intervention group. Subgroup 

analyses suggested improvements in SBP and DBP only for intervention subjects who produced the 

isoflavone metabolite equol, but the differences between equol and non-equol producers were not 

statistically significant. [88] To determine whether soy isoflavones reduce cardiovascular risk, research 

on soy isoflavone-rich foods in the context of an overall dietary pattern, rather than as a supplement to 

a Westernized diet, would be beneficial. Studies with larger samples are also warranted to explore the 

possibility of differential effects on the subset of equol-producers.

Sodium Reduction

Recommendation

18. In patients with hypertension or prehypertension, we recommend that sodium intake be

limited to no more than 2300mg/day (100mmol/day), with referral to a dietitian or other

support as appropriate. (Modified from 2004 VA/DoD HTN CPG)

Discussion

Many national and international organizations recommend reducing sodium intake for the prevention 

and management of hypertension, with the ultimate goal of reducing associated morbidity and 

mortality. 

There is a strong body of evidence from animal studies and human observational and experimental 

studies noting a dose-dependent relationship between dietary sodium intake and blood pressure in both 

normotensive and hypertensive individuals, though there is known variation in “salt sensitivity” both 

within and among populations. 

It should be noted that recommendations for dietary sodium reduction to reduce cardiovascular risk 

generally rely on surrogate markers (i.e., blood pressure) rather than clinical outcomes. The current 

guideline recommends a reduction to 2300mg/day. There is strong clinical evidence from the DASHSodium trial that a reduction from 3400mg (average daily intake of US adults) to 2300mg (the tolerable 

upper limit [UL] set by the Institute of Medicine [IOM] in 2005 [89]) improves blood pressure in the 

short term, [83] and limited observational research suggests cardiovascular disease event rates also 

decrease with reductions in sodium intake down to 2300mg. [90]

Only two relevant RCTs addressing blood pressure and/or mortality outcomes for reducing sodium 

intake met inclusion criteria for consideration in this CPG update. The Trials of Hypertension Prevention 

Phase II (TOHP II) study compared counseling on sodium reduction to usual care in overweight adults. 

[91] The intervention group achieved greater mean net decreases in SBP and DBP at both 18 and 36 

months; the effect was statistically significant when compared with controls for SBP at both times and 

for DBP at 18 months only. Shea et al. [92] presented mortality outcome data from a post-hoc analysis 

of the Trial of Nonpharmacologic Interventions in the Elderly (TONE). While the TONE study [93] itself is 

outside the a priori date parameters established for this CPG update, the efficacy of the intervention in 

reducing blood pressure should be noted when evaluating the subsequent mortality outcomes 

presented for the cohort. Despite clinically and statistically significant improvements in blood pressure, 
October 2014 Page 36 of 135

[93] no change in all-cause mortality was found for the intervention group when compared to usual 

care. [92] 

Both TOHP II and TONE were lifestyle interventions in free-living cohorts rather than controlled feeding 

trials. Thus, the low percentage of intervention group participants who met the studies’ goal of 

<80mmol/day (1840mg) average sodium intake (21% in TOHP II, roughly 40% in TONE) represents the 

inherent difficulty of lifestyle modification compounded by the ubiquity of sodium in the present US 

food supply. The studies support reducing sodium intake as a means to lower blood pressure, but do not 

justify a lower goal than 2300mg or confirm that clinical outcomes are improved. It is possible that an 

effect on mortality would have been detected had TONE intervention participants been more successful 

in lowering sodium intake.

Several organizations have specified lower targets for daily sodium intake. The 2010 Dietary Guidelines 

for Americans advise less than 1500mg sodium/day for individuals 51 years of age or older, and for 

select populations regardless of age (African Americans, hypertension, diabetes, or chronic kidney 

disease). [94] The American Heart Association’s Strategic Impact Goals for 2020 went further, identifying 

1500mg as a population-wide target, as the aforementioned salt-sensitive groups now comprise a 

majority of the US population. [95] Aside from the difficulty in limiting sodium to that extent without 

significant changes to the current food supply, this lower target is also controversial due to the lack of 

clinical outcomes data for reducing sodium to levels below 2300mg, and the suggestion of harm at low 

levels.

No studies demonstrating harmful effects of reducing sodium intake on either blood pressure or clinical 

outcomes met criteria for review during this CPG update. A 2013 IOM report evaluated the evidence on 

sodium intakes between 1500 and 2300mg, focusing on direct clinical outcomes. [96] The evidence 

reviewed was largely observational, though there were three Italian RCTs on heart failure patients which 

showed increased all-cause mortality [97] and/or adverse events [97-99] with lower sodium intakes (80 

vs 120mmol/day [1840 vs 2760mg]). The generalizability of these results is limited by significant 

discrepancies in participants’ medical treatment when compared with standard practice in the US 

(aggressive diuretic use and stringent fluid restriction); the reliability of two [97,98] of the three studies 

has since been questioned due to allegations of duplicate data. The IOM report concluded that sodium 

reduction at the population level is desirable to improve direct health outcomes, but that both the 

quantity and quality of evidence was insufficient to justify lowering sodium recommendations to 

1500mg/day for either the general public or for subgroups of the population. 

The average daily sodium intake in the US is over 3400mg/day excluding table salt, well above the more 

conservative recommendation of 2300mg/day. [100] Disagreement regarding the exact cut-point at 

which risks outweigh benefits should not distract from a unified public health message that a reduction 

in sodium intake from current levels is desirable. As dietary sodium recommendations rely heavily on 

research on surrogate markers, additional research is warranted to confirm that reducing blood 

pressure via reducing sodium intake has the predicted effect on morbidity and mortality. Future 

research is also needed to determine the efficacy and safety of lower sodium targets. 
October 2014 Page 37 of 135

Alcohol Reduction

Recommendation

19. We recommend advising hypertensive and prehypertensive patients to limit alcohol intake to

no more than 1 oz per day for men or 0.5 oz of alcohol per day for women. (This is

approximately 2 drinks/day in men and 1 drink/day in women, where a drink is 1.5 oz 80-proof

liquor, 12 oz beer, or 5 oz wine [all 14g]). (Modified from 2004 VA/DoD HTN CPG)

Discussion 

Alcohol use has a direct relationship with blood pressure, especially at levels of three or more standard 

drinks per day (≥34 grams of ethanol per day). [101] In patients with chronic alcoholism, cessation of 

alcohol use has been shown to reduce blood pressure and prevalence of hypertension. [102] Patients 

with hypertension and alcohol dependence who receive regular counseling to reduce their alcohol 

intake have a small, but significant, reduction in their blood pressure. [103] For patients with 

hypertension and excessive alcohol intake, it is reasonable to recommend reduction of alcohol intake to 

a maximum of two drinks per day for men and one drink per day for women. A structured counseling 

program can increase adherence to reduction or abstinence of alcohol intake. 

Pharmacological Therapy 

Treatment of hypertension with drugs in clinical trials has reduced stroke incidence by 35 to 40%; 

myocardial infarction by 20 to 25%; and HF by more than 50%. [104] While most hypertensive patients 

benefit from pharmacotherapy, this benefit is larger among patients who already have complications of 

hypertension, such as target organ damage. For example, in the presence of CVD or target organ 

damage, only nine patients would require such BP reduction to prevent one death. [16] Similarly, in

SHEP, HF was reduced by 49% with drug treatment in all patients, while it was reduced by 81% in those 

with a prior myocardial infarction. [105] 

Initiation of Pharmacotherapy

A reference table for blood pressure thresholds to initiate pharmacotherapy can be found in Appendix 

D. Detailed recommendations and discussion can be found below. 

Systolic Blood Pressure Thresholds

Recommendations 

20. We recommend offering pharmacologic treatment for hypertensive patients 60 years and older

with a systolic blood pressure ≥ 160 mmHg.

21. We suggest considering pharmacologic treatment using a shared decision-making model for

hypertensive patients 60 years and older with systolic blood pressure <160 mmHg.

22. We suggest offering pharmacologic treatment to patients with a history of cerebrovascular

disease (stroke, transient ischemic attack, or asymptomatic carotid artery disease) and a

systolic blood pressure ≥140 mmHg.
October 2014 Page 38 of 135

23. We suggest pharmacologic treatment for hypertensive patients younger than 60 with a systolic

blood pressure ≥160 mmHg, regardless of diastolic blood pressure.

Discussion

The recommendation for initiation of pharmacologic therapy to reduce blood pressure at systolic blood 

pressure greater than or equal to 160 mmHg for patients with hypertension is based on the evidence for 

reduction in clinical events from randomized control trials. Nearly all of the evidence is from clinical 

trials which enrolled a majority of patients starting at age 60 years of age or older. Multiple studies, such 

as SHEP, Medical Research Council (MRC) Working Party, and Hypertension in the Very Elderly Trial

(HYVET), have demonstrated a reduction in the risk of stroke with treatment of systolic hypertension in 

elderly populations. [106-109] The HYVET study, which enrolled individuals age 80 or older with a 

systolic blood pressure of at least 160 mmHg and randomized subjects to either active pharmacologic 

treatment or placebo, demonstrated a significant 21% relative reduction in all-cause mortality and a 

23% relative reduction in cardiovascular mortality after only a median of 1.8 years of treatment. [110] 

During a one year extension of the main trial, this reduction was found to be durable. [106] Several 

studies enrolled patients starting at age 60 (European Working Party, SHEP, Systolic Hypertension in 

Europe [Syst-Eur]) or age 65 (MRC Working Party) with SBP of at least 160 mmHg. Both the European 

Working Party [111] and SHEP trials [112] demonstrated significant reductions in cardiovascular 

mortality. 

Only one study, the Hypertension-Stroke Cooperative Study, initiated treatment at an SBP of 140 mmHg

or higher, and enrolled stroke survivors; but it did not demonstrate a reduction in stroke with active 

treatment, only a small reduction in heart failure. [113] This study is limited by its small sample size; 

therefore, any clinically significant effect on stroke could have been missed. This was also the only study 

included in our evidence base that included African Americans treated at a threshold below 160 mmHg. 

The benefit of treatment on stroke reduction or cardiovascular events in the Hypertension-Stroke 

Cooperative Study was not larger for African Americans than for whites with systolic blood pressure 

between 140 and 220 mmHg. Furthermore, data were stratified by baseline blood pressure. Among 

subjects with an SBP between 140 and 160 mmHg, no benefit of medication was observed (20.5% in the 

active medication group vs. 20.9% in the placebo group for stroke or cardiovascular events). While this 

analysis was not further stratified by race, about 80% of these study subjects were African American, 

suggesting that treating at a lower threshold of 140 mmHg may not be beneficial, even among African 

Americans. As African Americans have a higher prevalence of hypertension and have a higher incidence 

of stroke, it is important to assess whether the threshold for treatment should be lower in this 

population. This may be an area for future research. 

Only one study in the evidence base enrolled patients younger than age 60 without a history of stroke. 

This was the Oslo study, [114] which enrolled relatively healthy subjects age 40-49 years with an SBP of 

150-179 mmHg and randomized them to either usual care (control group) or active treatment with 

hydrochlorothiazide with or without methyldopa or propranolol. The difference in change in mean SBP 

was 17 mmHg between the active treatment and control groups. No difference in major cardiovascular 

events or mortality was seen between the two groups, thus limiting the base of evidence to make 

recommendations for SBP thresholds for people less than 60 years based on outcomes other than 
October 2014 Page 39 of 135

surrogate outcomes, such as blood pressure. This study did not, however, demonstrate significant harm 

associated with the treatment of these younger patients. 

The recommendations for suggested treatment at age less than 60 years or for SBP between 140 mmHg 

and 159 mmHg for individuals over 60 years were made based on potential benefit for reduction in 

cardiovascular events and low patient burden associated with pharmacologic treatment. However, given 

the lack of evidence from RCTs with outcomes other than intermediate outcomes (achieved BP) to 

support this recommendation, pharmacologic therapy should only be instituted after a discussion with 

the patient about his or her own values and preferences with regard to treatment of hypertension and 

prevention of hypertension-related disease. 

Despite the recommendation of a systolic blood pressure threshold of 160 mmHg for the initiation of 

pharmacologic therapy, lifestyle modifications can and should be instituted, if not contraindicated, for 

adults at any age with a SBP value above 120 mmHg, both for the prevention of hypertension and 

because lifestyle modification therapies can potentially be associated with other favorable health 

outcomes and are unlikely to result in harm. 

Research priorities should focus on examining outcomes for patients 60 years and older when 

pharmacologic therapy for hypertension is initiated at a SBP of less than 160 mmHg. A systolic BP 

threshold trial in patients younger than age 55 years would be difficult to conduct given that patients in 

this age group often have either diastolic hypertension or combined systolic/diastolic hypertension.

While the currently ongoing Systolic Blood Pressure Intervention Trial (SPRINT) trial includes some 

participants <60 years of age (55 years and older), and has a SBP entry threshold of 130 mmHg, it is 

testing SBP goals of 120 mmHg vs <140 mmHg. [115] and will not test different thresholds for initiation 

of therapy. 

Diastolic Blood Pressure Thresholds

Recommendation 

24. We recommend offering pharmacologic treatment for patients 30 years and older with a

diastolic blood pressure ≥90 mmHg.

25. We suggest offering pharmacologic treatment for patients age 18 to 29 with a diastolic blood

pressure ≥90 mmHg.

Discussion

For most populations, the initiation threshold and target diastolic blood pressure of 90 mmHg is wellestablished. Multiple studies have demonstrated cardiovascular benefit for patients with treatment of 

diastolic hypertension in patients older than 60. [107,111,116] The Department of Veterans Affairs 

Cooperative Studies demonstrated a significant reduction in cardiovascular morbidity when 

antihypertensive pharmacologic therapy was initiated in a middle-aged male Veteran population whose 

DBP was 90-129mmHg. [117],[118] Subsequently, the Australian National BP study [119] demonstrated 

a reduction in fatal and nonfatal cardiovascular events when pharmacologic therapy was instituted 

when the DBP was 95-109 mmHg in a young, healthy population. Similarly, the National Institutes of 

Health (NIH) randomized nearly 11,000 diverse patients in a five-year trial comparing sequential care 
October 2014 Page 40 of 135

versus routine community care. This was not placebo-controlled, and most community-care patients 

did, in fact, receive treatment for their hypertension, particularly in the higher baseline diastolic strata 

(105-114 mmHg, and 115 mmHg –plus, respectively). [120] In the predefined stratum of 90-104 mmHg

baseline DBP, significant reductions in all-cause mortality and stroke were noted, approaching nonhypertensive population levels in the subgroup analyses. [121] There is evidence that all patients, 

regardless of age, with CKD or cerebrovascular disease (CVA, transient ischemic attack, carotid disease) 

derive mortality benefit with treatment for DBPs above 90 mmHg. [122,123] 

There are no outcome studies published evaluating patients younger than age 30, so an appropriate 

threshold for initiating antihypertensive pharmacologic treatment is not clear. In this younger 

population, it may be appropriate to recommend a three to six month period of therapeutic lifestyle 

modification prior to offering medication management when their DBP is 90mmHg or higher. 

Blood Pressure Goals

A reference table for blood pressure goals can be found in Appendix D. Detailed recommendations and 

discussion can be found below. 

Systolic Blood Pressure Goals

Recommendations 

26. For patients 60 years and over, we recommend treating to a systolic blood pressure goal of

<150 mmHg.

27. For patients below 60 years of age, we suggest treating to a systolic blood pressure goal of

<150 mmHg.

Discussion

The evidence supporting treating to a SBP goal less than 150 mmHg is strong and is based on several 

well-done randomized placebo-controlled trials in participants aged 60 and above with isolated systolic 

hypertension [109,124] and in hypertensive participants aged 80 and above. [110] These trials 

demonstrated significant benefits for major cardiovascular outcomes, and HYVET also demonstrated 

reduction in mortality. [110] Another placebo-controlled trial demonstrated benefits in major 

cardiovascular outcomes for a SBP goal less than 160 mmHg. [125] Other major outcome trials 

comparing a lower SBP goal (130-140 mmHg) to a higher SBP goal (140 to 160 mmHg or 140 to 149 

mmHg) in older participants [126,127] and participants with a recent lacunar stroke [128] failed to 

demonstrate significant reduction in major cardiovascular events for the lower goal compared to the 

higher goal, although these trials did not conclusively disprove any benefit.

Although there is little evidence to support the previous recommendations to treat this population to a 

SBP goal of <140 mmHg, there is also little evidence for harm. For patients who are well-managed below 

140 mmHg, not on a complex regimen and tolerating it well, it is not necessary to reduce therapy to try 

to aim for a target between 140 and 150 mmHg. However, for newly diagnosed patients, achieving a 

systolic goal of <150 mmHg is feasible and may require fewer resources than the previously 

recommended goal of 140 mmHg. 
October 2014 Page 41 of 135

The committee has a high degree of confidence in the quality of the existing evidence. A high priority for 

research is determining if lower SBP goals are beneficial or harmful in this older population. One such 

trial already underway is the SPRINT, sponsored by the National Heart, Lung, and Blood Institute (NHLBI) 

and expected to be completed by 2016-17. [115] It is testing whether an SBP goal of <120 mmHg

reduces major cardiovascular and renal events, and dementia compared with an SBP goal of <140 mmHg

in >9,000 high-risk non-diabetic patients, most of whom will be age ≥60 years with an SBP ≥130 mmHg. 

Recommendation 27 is based on expert opinion interpretation of indirect evidence, since there are no 

major outcome trials in our review for non-diabetic, non-CKD hypertensive patients testing a specific 

SBP goal in persons younger than 60 years. In the absence of such evidence, and the stronger 

relationship between DBP and cardiovascular risk in younger persons, the committee suggests an SBP 

treatment goal of less than 150 mmHg in this population; an SBP goal of <150 mmHg has been 

demonstrated to reduce cardiovascular outcomes in patients above age 60 years and in patients with 

diabetes. The average achieved SBP will likely be much lower when recommended DBP goals are 

reached in this population. In DBP goal studies in this middle-aged and younger population, the achieved 

SBP levels averaged less than 140 mmHg. Therefore, as in the older population, for patients whose SBP 

is below 140 mmHg, and not on a complex regimen and tolerating the medications well, there is little 

evidence for harm and it is not necessary to reduce therapy to try to aim for a target between 140 and 

150 mmHg if the DBP goal has been achieved.

Patients in this age group may prefer a lower SBP goal, since other guidelines recommend an SBP goal of 

<140 mmHg. Providers should discuss with these patients that there is little evidence for either 

additional harm or benefit for this lower goal, pending ongoing trials. Although an SBP goal of <140 

mmHg may be desirable, there are no previous or current RCTs comparing a goal of <150 mmHg to <140 

mmHg or other lower goals. 

For patients with CKD and hypertension, refer to the VA/DoD CKD CPG4 which recommends a SBP goal 

of <140 mmHg. 

Diastolic Blood Pressure Goals

Recommendation

28. We recommend treating to a diastolic blood pressure goal <90 mmHg in patients 30 years and

older.

29. We suggest treating to a diastolic blood pressure goal <90 mmHg in patients age 18 to 29.

Discussion

Strong clinical trial evidence exists demonstrating the benefits of treating hypertension to a DBP goal of 

less than 90 mmHg. Landmark studies such as the Veterans Administration Cooperative Study Group on 

Antihypertensive Agents, the Hypertension Detection and Follow-up Program (HDFP), and the MRC trial

of treatment of mild hypertension all demonstrate substantial benefits in terms of reduced 

4 See the VA/DoD Clinical Practice Guideline for the Management of Chronic Kidney Disease. Available at: 

http://www.healthquality.va.gov/guidelines/cd/ckd/index.asp
October 2014 Page 42 of 135

cardiovascular events by treating to a target DBP of less than 90 mmHg. [117,118,120,122,129] Eligibility 

for these studies differed slightly, but generally included patients 30 years of age or older. In the 

Hypertension Optimal Treatment (HOT) trial, further reductions below 90 mmHg were not shown to be 

of benefit. In HOT, over 18,000 patients with diastolic blood pressures between 100 and 115 mmHg

were randomized to target DBPs of ≤90, ≤85, or ≤80 mmHg. No significant differences among the groups 

were noted for a broad range of cardiovascular endpoints. [130] In the absence of specific evidence for 

DBP goals in patients age 18 to 29, it is reasonable to extrapolate the data from older populations to this 

younger group.

Specific Populations

Diabetic Population

Recommendations 

30. For patients with diabetes (all age groups), we recommend treating to a systolic blood pressure

goal of <150 mmHg.

31. For patients with diabetes (all age groups) who tolerate antihypertensive drugs, we suggest

treating to a systolic blood pressure goal of <140 mmHg.

32. For patients with diabetes, we recommend treating to a diastolic blood pressure goal <85

mmHg.

Discussion

Recommendation 30 is based on moderate quality evidence from three SBP-goal RCTs [109,124,131] 

that treatment to an SBP goal of <150 mmHg improves major cardiovascular and cerebrovascular 

outcomes and lowers mortality in adults with diabetes and hypertension. No RCT addressed whether 

treatment to an SBP goal of <140 mmHg compared with a higher goal is beneficial in adults with 

diabetes and hypertension. Only the Action to Control Cardiovascular Risk in Diabetes (ACCORD) BP trial 

[132] compared an SBP goal lower than 140 mmHg (<120 mmHg) with a higher SBP goal (<140 mmHg) in 

patients with diabetes and hypertension. ACCORD BP did not show significant benefit for the primary 

cardiovascular disease outcome for the SBP <120 mmHg group, but did show a reduction in stroke and 

an increase in serious adverse events. This was not sufficient evidence to support a lower SBP goal in 

diabetes.

Recommendation 31, suggesting an SBP goal of <140 mmHg for patients with diabetes who tolerate 

antihypertensive medications, is supported by the <140 mmHg SBP goal control group in the ACCORD BP 

trial, [132] in which this control group (SBP goal of 140 mmHg) had similar cardiovascular outcomes but 

fewer serious adverse events than the lower SBP goal group, and the Action in Diabetes and Vascular 

Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, [133] which showed that 

mortality was reduced with a combination of a thiazide-type diuretic and an angiotensin-converting 

enzyme inhibitor (ACEI) to lower blood pressure in persons with diabetes mellitus. (In the ADVANCE 

trial, although there was not an SBP goal, the mean achieved SBP of 135 mmHg is consistent with an SBP 

goal of <140 mmHg.)
October 2014 Page 43 of 135

Achieving these goals is feasible and should require fewer resources than the recommended goal of 

<130 mmHg in diabetes in many previous guidelines (but not the 2004 VA/DoD Hypertension CPG which 

recommended <140 mmHg). Patients may prefer a lower SBP goal than 150 or 140 mmHg, since 

previous guidelines in the past decade have recommended a lower SBP goal. Providers should discuss 

with these patients to determine the best balance between a decreased stroke risk, but higher adverse 

effect risk, with a lower goal (as shown in the ACCORD BP trial [132]). A trial testing a SBP goal lower 

than 150 mmHg (e.g., 120 or 130 mmHg) in patients with diabetes mellitus is a high research priority 

and would be feasible and ethical to undertake, since ACCORD BP did not prove that the lower goal was 

not beneficial due to the unexpected reduced power (from low event rates) and a wide confidence 

interval for the primary outcome that included a clinically important benefit.

Results from randomized clinical trials demonstrate that more intensive therapy of diastolic blood 

pressure to levels below that in the general population is of benefit in hypertension patients with 

diabetes. The strongest evidence is provided by the UK Prospective Diabetes Study Group. [134] Patients 

with a mean blood pressure of 160/94 mmHg at baseline were randomized to tight control (target blood 

pressure <150/85 mmHg) versus less tight control (target blood pressure <180/105 mmHg). Tight 

control was associated with reduced risk of important outcomes including death due to diabetes and 

stroke. While this was not a direct comparison of a target of 90 mmHg versus a lower goal, the achieved 

blood pressure was 144/82 mmHg in the tight control group versus an achieved blood pressure of 

154/87 mmHg in the group with less tight control. The HOT study was a direct comparison study. [130] 

Diabetic and non-diabetic patients with DBPs between 100 and 115 mmHg were randomized to target 

DBPs of ≤90, ≤85 or ≤80 mmHg. Achieved blood pressures were 85.2, 83.2, and 81.1 mmHg respectively. 

Among patients with diabetes, intensive treatment was associated with significant declines in major 

cardiovascular events. The relatively small diabetes sub-sample, and the fact that the analysis of 

patients with diabetes was not pre-specified, limits the strength of this evidence. It should be noted that 

the VA/DoD Management of Diabetes Mellitus in Primary Care CPG recommends a DBP goal of 80 

mmHg due to more weight being placed on the HOT study.5

 

Elderly Population

Particular uncertainty exists surrounding blood pressure treatment goals in very old patients with 

hypertension. Clinical trials such as SHEP and HYVET provide strong evidence for the benefits of 

treatment to guideline-recommended levels in at least some elderly hypertension patients. However, it 

is important to recognize that these clinical trials included relatively few people over age 85 and those 

elderly included in the study may have been healthier than “average.” [135] This raises questions as to 

the generalizability of these results to broad segments of the elderly population. Moreover, extensive 

population-based data suggest that higher blood pressure is associated with enhanced survival in people 

over age 85. [136] While these conflicting results cannot be fully reconciled, recent observational studies 

suggest that frailty and comorbidity should perhaps be considered when setting treatment goals in the 

very old. Among elderly patients in the National Health and Nutrition Examination Survey (NHANES) 

5 See the VA/DoD Clinical Practice Guideline for the Management of Diabetes Mellitus in Primary Care. Available 

at: http://www.healthquality.va.gov/guidelines/CD/diabetes/
October 2014 Page 44 of 135

sample, higher SBP was associated with increased mortality in those with a fast gait speed, while in 

people with a slow gait speed there was no association between mortality and blood pressure. In those 

unable to do the walk test, higher SBP was associated with a lower risk of death. [137] Similarly, in the 

Leiden 85-Plus Study, higher SBP was associated with a lower risk of stroke in those subjects with 

physical and cognitive impairment. [138] Further guidance on treatment goals for frail, elderly 

hypertension patients will require additional clinical trials. For now, clinicians should exercise their 

judgment in setting treatment goals for these patients.

Hypertension Control and Follow-up

Control, Adherence, and Presence of Adverse Effects

Recommendation 

33. We suggest that patients be seen within one month of initiation of lifestyle or pharmacological

therapy to determine adequacy of hypertension control, degree of patient adherence, and

presence of adverse effects. (Modified from 2004 VA/DoD HTN CPG without an updated

systematic review of the evidence.)

Discussion

Some medications may have a rapid onset of blood lowering pressure, but the full antihypertensive 

effect may take a month or more. Seeing these patients within a month may help stress to these 

patients the importance of their diagnosis, and may help the clinical care team to assess how well the 

patient is adhering to his or her therapy. In addition, the provider can discuss with the patient any side 

effects he or she may be having from the medication or other challenges he or she may have with 

adherence to treatment. 

Although the initiation of treatment belongs firmly in the hand of the credentialed provider, other 

members of the healthcare team can serve a valuable role in the follow-up of these newly diagnosed 

patients. Patient education, assessment of adherence and the assessment of potential adverse effects 

can easily be done by their skill set, freeing up the clinician to see the more resistant cases and the 

patients where titration of therapy is necessary. The implementation of the Patient Centered Medical 

Home (PCMH) model also supports the elevation of primary care staff to functioning at the top of their 

licensure. 

Follow-up Once Hypertension is Controlled

Recommendation

34. Once the patient’s blood pressure is controlled, we suggest follow-up at least annually, or more

frequently as indicated, depending on patient preference. (Modified from 2004 VA/DoD HTN

CPG without an updated systematic review of the evidence.)

Discussion

There is no definitive evidence on what duration between follow-up visits helps maintain optimal blood 

pressure, although a study by Birtwhistle et al. suggested that six month visits yielded similar control to 

three month visits. [139] However, in that study, because patients were free to visit their clinician at any 
October 2014 Page 45 of 135

time, the number of visits over the approximately three-year study period was roughly similar (16.2 vs. 

18.8 visits) although statistically significant. Hence, any interval within that timeframe would generally 

be appropriate; depending on clinical circumstances some patients may be seen earlier or later. 

Without evidence to show that more frequent visits are beneficial to patients, our recommendation is 

that well-controlled, uncomplicated patients be seen at least annually. Patients should be instructed to 

contact their care providers in the interim if they experience any side effects or have any other 

challenges with continuing their therapy.

Cessation of hypertensive therapy

Decrease or cessation of antihypertensive drug therapy is possible in patients who are willing to do so, 

and whose BP is well below goal. These patients should be closely followed-up.

Although hypertension is frequently considered to be a life-long diagnosis, there is the potential to 

reduce the number or dosage of drugs for patients who have been under good control for an extended 

period of time, or if they have made new significant changes in their lifestyle or body weight. This 

reduction in medication is most likely to be successful if the BP control has been accompanied by one or 

more changes in the patient’s weight, diet and/or activity level. If the medications were started in a 

stepwise manner, it is unlikely that a reduction in the dosage or number of medications will be 

successful without a change in some of the underlying lifestyle habits that are known to lead to 

increased blood pressure.

Regarding completely stopping hypertensive therapy, a review of observational data from the Second 

Australian National Blood Pressure Study (ANBP2) cohort suggests that those most likely to successfully 

withdraw from antihypertensive medication are patients whose blood pressures are controlled with 

monotherapy. [140] When withdrawal of therapy does occur, follow-up should generally be tailored to 

shorter durations at first to assure that blood pressure does not rise again.

Referrals to specialists

From a clinical perspective, referral to, or consultation with, hypertension specialists or those with 

particular expertise in the relevant clinical area should be considered if there is failure to achieve target 

blood pressure goals when the patient is on appropriate doses of three medications (one of which 

should typically be a thiazide-type diuretic and assuming that other remedial causes of inadequate 

response have been identified and addressed) or there is a suspected secondary cause for hypertension.

The vast majority of hypertensive patients can be successfully managed within DoD and VA primary care 

clinics. However, there are cases when patients will not reach their blood pressure target, even after 

having been prescribed three or more medications at recommended doses. If patient non-adherence

and white coat effect have been ruled out, then further work-up should be done to determine if there is 

any treatable cause for this “resistant hypertension.” Although a primary care provider can test for and 

treat a few of the causes of resistant secondary hypertension, others require specialist intervention.

Referring a patient to, or consulting with, a hypertensive specialist can help direct the diagnostic workup and treatment of these patients. Referral to a specialist need not wait until the patient is on three
October 2014 Page 46 of 135

antihypertensive agents at maximal doses if clear signs/symptoms of a cause of secondary hypertension 

are present. 

Resistant and Secondary Hypertension

An early discussion or consultation with an appropriate specialist is encouraged when a patient has 

resistant hypertension or is suspected of having secondary hypertension due to such conditions as 

primary kidney disease, Cushing’s, or pheochromocytoma. Refer to Table 5 for a list of the most 

common causes of secondary hypertension. 

Secondary forms of hypertension may be present in up to 10% of all cases of hypertension. [141-143] In 

cases of resistant hypertension, a contributing cause such as sleep apnea, [144] hyperaldosteronism, 

[145,146] Cushing’s syndrome, [147] or kidney disease [148,149] is present in the majority of cases and 

a targeted evaluation based on the patient’s risk factors and clinical history should be undertaken.

Recent estimates suggest that more than 20% of hypertensive patients meet criteria for resistant 

hypertension in the US, [150] so evaluation for causes of secondary hypertension will become a more 

common practice, even in the primary care setting. Referral to appropriate experts, as needed, may lead 

to the most accurate and cost-effective evaluation for secondary hypertension.

Table 5. Recommended Testing for Patients Suspected of Having Secondary Hypertension

Disease Features Recommended Test/Referral

Obstructive Sleep 

apnea

Daytime somnolence 

Fatigue

Obesity

Snoring or observed 

apneic episodes

Referral for overnight 

polysomnagram (sleep study)

Drug or substance 

Induced

Nonsteroidal antiinflammatory drugs 

(NSAIDs), including Cox-2 

Inhibitors

Sympathomimetics (e.g., 

decongestants, 

anorectics)

Combined oral 

contraceptives 

Adrenal steroids 

Erythropoietin 

Cyclosporine, tacrolimus 

Cocaine, amphetamines 

Excessive alcohol use 

Licorice

Selected dietary 

supplements (e.g., ma 

huang, ephedra, bitter 

orange)

History

Urine toxicology as indicated

Primary 

hyperaldosteronism

Resistant Hypertension

Hypokalemia

Plasma aldosterone and plasma 

renin activity
October 2014 Page 47 of 135

Disease Features Recommended Test/Referral

Consider referral for an elevated 

aldosterone/renin ratio

Kidney disease Elevated serum creatinine 

Proteinuria 

Hematuria on two 

occasions or structural 

renal abnormality (e.g., 

abdominal or flank 

masses)

Abnormal urine sediment 

Urinalysis; estimation of urinary 

protein excretion and creatinine 

clearance by using a single 

random urine test; renal 

ultrasound may also be 

considered

Consider referral to nephrology

Renovascular disease Abdominal bruits over the 

renal arteries

Abrupt onset of severe 

hypertension 

Diastolic BP >115 mmHg

Initial onset age <50 years 

Worsening BP control 

when previously stable

Evidence of 

atherosclerotic vascular 

disease

Hypertension

There are a variety of screening 

tests for renovascular 

hypertension, depending on 

equipment and expertise in 

institutions

Renal Artery Doppler 

Ultrasound, Computerized 

tomography (CT) Angiography, 

Magnetic resonance 

Angiography, and post-captopril 

renograms are used

However, there is no single best 

test for renovascular 

hypertension, and consultation 

with experts in your institution 

is recommended

Intravenous pyelogram is 

relatively contraindicated in 

diabetes and no longer 

recommended as screening test 

for renovascular disease.

Cushing’s syndrome

and other

glucocorticoid excess

states including

chronic steroid

therapy

Amenorrhea

Increased dorsal fat

Diabetes mellitus 

Edema

Hirsutism 

Moon facies 

Purple striae 

Truncal obesity

History

24-hour urine for free cortisol

Dexamethasone suppression 

test

Late night salivary cortisol

Consider referral to a specialist

Hyperthyroidism Anxiety

Brisk reflexes

Hyperdefecation

Heat intolerance

Tachycardia 

Tremor

Weight loss

Thyroid Stimulating Hormone 

(TSH) 

Free T4
October 2014 Page 48 of 135

Disease Features Recommended Test/Referral

Wide pulse pressure

Aortic Coarctation Weak or delayed femoral 

pulses

Echocardiogram

Computerized tomography 

angiography

Pheochromocytoma Labile BP

Orthostatic hypotension

Paroxysms

(headaches,

palpitations, sweating, 

pallor) 

Tachycardia

Plasma metanephrines or 24-

hour urine for metanephrines

and/or catecholamines

Consider referral to specialist

Hyperparathyroidism Hypercalcemia

Polyuria/polydipsia

Renal stones

Serum calcium and parathyroid

hormone (PTH) level

Monotherapy or Combination Therapy

Recommendations 

35. We suggest taking into consideration the patient’s baseline blood pressure and presence of

comorbidities, when deciding on either monotherapy or combination therapy (two drugs)

when initiating drug therapy. (Modified from 2004 VA/DoD HTN CPG without an updated

systematic review of the evidence.)

36. We suggest initiating combination therapy for patients with a baseline systolic blood pressure

of >20 mmHg or diastolic blood pressure of >10 mmHg above the patient’s goal. (Modified from

2004 VA/DoD HTN CPG without an updated systematic review of the evidence.)

Discussion

Different approaches to initial treatment of hypertension, either with a single agent or combination 

therapy, are appropriate as long as the goal blood pressure is achieved. Evidence is lacking to suggest a 

benefit in primary outcomes of interest to include mortality, cardiovascular events, stroke, or adverse

effect profiles of one treatment approach compared to another. We recommend the provider consider 

each patient’s comorbid conditions and degree of blood pressure lowering desired when selecting initial 

therapy. 

Evidence from the Avoiding Cardiovascular Events in Combination Therapy in Patients Living with 

Systolic Hypertension (ACCOMPLISH) confirms that combination therapy is safe and effective, [151] and 

evidence from ALLHAT confirms that combination therapy is required in a majority of patients to reach 

blood pressure goals. [152] Only 26% of participants reached goal blood pressure (<140/90 mmHg) with 

a single antihypertensive drug, even after adjustment in dosage. [153] Although evidence is lacking to 

recommend a firm threshold for initiating combination therapy, we observe that a desired reduction of 

blood pressure of 20/10 mmHg will often require at least two medications to achieve BP control, and 

that initiating therapy with two drugs appears to be well tolerated in most patients. Patients with a 

compelling indication for more than one class of antihypertensive agent may benefit from initial 
October 2014 Page 49 of 135

combination therapy as well. Although the evidence review for this update did not include studies with 

primary outcomes of medication adherence, time to blood pressure control, or overall effectiveness of 

reaching goal blood pressure, the committee suggests that these measures may be improved with initial 

combination therapy.

In summary, the best outcomes result from achievement of goal blood pressure. As a majority of 

patients will require more than one medication to achieve goal, we suggest initial therapy with two 

medications of different classes for patients with an SBP of >20 mmHg or DBP of >10 mmHg or more 

above goal. However, no two renin-angiotensin system (RAS) blockers should be used together (Refer to 

Recommendations 43 and 44). 

First-line Therapy

Recommendation

37. We recommend the use of thiazide-type diuretics for the treatment of hypertension.

38. We suggest the use of thiazide-type diuretics at recommended treatment doses as first-line

therapy for drug treatment of hypertension either as monotherapy or in combination with

other agents. (Modified from 2004 VA/DoD HTN CPG)

Discussion

Similar to past guidelines, evidence supporting initiating antihypertensive therapy with a thiazide-type 

diuretic is based primarily on many placebo-controlled outcome trials with thiazide-type diuretics as the 

basis of therapy and results from the ALLHAT trial, [154] which is especially pertinent to VA/DoD

providers due to the >7,000 Veterans included in the study. New evidence has been published in the 

ACCOMPLISH study favoring ACEI/calcium channel blocker combination over an ACEI/thiazide-type 

diuretic combination. [151] While this evidence was considered for this recommendation, the dose of 

the thiazide-type diuretic in ACCOMPLISH (hydrochlorothiazide 12.5-25 mg/day) is lower than 

equipotent doses of chlorthalidone or indapamide. [151] Due to this finding, thiazide-type diuretics 

should be prescribed at the doses which demonstrated greatest clinical benefit from randomized 

controlled trials. While the cost differential between all initial therapies has closed significantly since the 

2004 VA/DoD HTN CPG was published, thiazide-type diuretics remain a cost-effective first choice. 

Although ACCOMPLISH has weakened the strength of this recommendation, there remains strong 

evidence to support the use of thiazide-type diuretics as first-line therapy.

Thiazide-type Diuretics

Recommendations 

39. To initiate treatment of hypertension with a thiazide-type diuretic, we suggest the use of

chlorthalidone or indapamide over hydrochlorothiazide.

40. We do not suggest switching from hydrochlorothiazide to chlorthalidone or indapamide if the

patient is adequately controlled on and tolerating hydrochlorothiazide.

41. We suggest considering a switch from hydrochlorothiazide to chlorthalidone for patients whose

hypertension is inadequately controlled on 50mg/day of hydrochlorothiazide.
October 2014 Page 50 of 135

42. We recommend a dosage of 12.5-25mg/day of chlorthalidone, 25-50mg/day of

hydrochlorothiazide, or a dosage of 2.5mg/day immediate-release or 1.5-2.5mg/day sustainedrelease (not currently available in the US) of indapamide.

Discussion

The justifications for these recommendations are based on the level of blood pressure reduction and the 

drugs doses which have reduced major outcomes in RCTs for hydrochlorothiazide (HCTZ), chlorthalidone 

and indapamide. For initial or add-on treatment of hypertension, chlorthalidone and indapamide result 

in greater decreases of blood pressure compared to current low doses (12.5-25mg/day) of HCTZ. [155-

160] There is limited evidence which suggests that HCTZ at doses of 37.5-60mg/day provides similar BP 

as chlorthalidone 12.5-60mg/day. [160,161] Additionally, the effect of HCTZ only lasts about 16 to 24 

hours, while the action of chlorthalidone is about 48 to 72 hours. This difference could have a more 

stable effect on blood pressure and partially explain the larger effect of chlorthalidone in preventing 

cardiovascular events. [162] In general, indapamide and chlorthalidone at recommended doses appear 

to provide additional reduction in SBP (4-5 mmHg) and DBP (2-3 mmHg) compared to low doses of HCTZ 

(12.5-25mg/day). There is limited evidence for direct comparisons of blood pressure reduction between 

chlorthalidone and indapamide; however, they appear to be similar at the doses we have 

recommended. [163] A variety of doses and formulations of indapamide have been used in studies. 

Indapamide immediate-release (IR) appears to provide the greatest blood pressure reduction at 

2.5mg/day, but based on the differences in study designs, a specific dose of the sustained-release (SR) 

formation could not be recommended. Therefore we have listed a dose range of 1.5-2.5mg/day. It 

should be noted that the SR formulation of indapamide is not currently available in the US.

There are no randomized controlled trials comparing HCTZ, chlorthalidone, and indapamide to each 

other, or at different doses, on clinical outcomes such as overall mortality, cardiovascular mortality and 

stroke. 

Changes in serum electrolytes, specifically potassium, were measured in several studies; there is no 

clear evidence of clinically significant differences between these three thiazide-type diuretics at 

comparable therapeutic doses based on the available evidence either in the general hypertensive 

population or in the elderly. [158,160,161] 

Thiazide-type diuretics were found to be safe and effective for the treatment of hypertension in patients 

with mild chronic kidney disease. Thiazide-type diuretics may be less effective in patients with serum 

creatinine above 2mg/dL or creatinine clearance less than 30mL/min, as patients with moderate to 

severe kidney disease were largely excluded from these clinical studies.

We considered making a stronger recommendation for chlorthalidone or indapamide based on the 

evidence; however, when considering the values of patients and providers we recognized the reasons 

why it may be difficult to change therapy from HCTZ or to initiate therapy with another thiazide. HCTZ is 

well known to both patients and providers and is incorporated into a variety of combination products, 

especially those including ACEIs and angiotensin II receptor blockers (ARBs) that are commonly used in 

practice. In contrast, chlorthalidone and indapamide are only available in a limited number of 
October 2014 Page 51 of 135

combination products. We also recognize that many providers may be hesitant to prescribe HCTZ in 

doses greater than 25mg/day based on their training or clinical experience; however, we point out the 

lack of positive outcome data for HCTZ at doses of 12.5-25mg/day when compared to other agents.

Given the proven safety and outcome benefits of thiazide-type diuretics and the low cost of select 

thiazide-type diuretics, specifically HCTZ and chlorthalidone, these agents should continue to be a major 

component of the treatment of hypertension; however, we currently have limited outcome data to 

compare the specific thiazide-type diuretics to each other. A research priority should be to provide 

comparative effectiveness data, preferably via randomized controlled trials focusing on the important 

patient outcomes of overall mortality and cardiovascular morbidity and mortality.

Alternative or Supplementary Therapies

Recommendation

43. We recommend using the following as alternative therapies for patients who cannot tolerate

thiazide-type diuretics, as supplementary therapies for patients who do not reach their

hypertensive goals, or for those starting on combination therapy:

a. Angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers (but not

together)

b. Long-acting dihydropyridine calcium channel blockers

(Modified from 2004 VA/DoD HTN CPG)

Discussion 

ACEIs and ARBs have shown benefit in reducing CVD morbidity in patients with hypertension, and either 

drug class is recommended. In addition, ACEIs have well-established benefits when used in patients with 

reduced ejection fraction heart failure, left ventricular systolic dysfunction, post MI, and in patients with 

diabetic and non-diabetic CKD.

In the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint (ONTARGET) headto-head trial of an ACEI (ramipril) vs. an ARB (telmisartan), no differences were reported in renal or 

cardiovascular (CV) outcomes (composite endpoint of CV death, myocardial infarction, stroke or heart 

failure hospitalization) in a population of patients with vascular disease, of whom 69% were 

hypertensive. [164] Other data support the use of ARBs. The composite of cardiovascular morbidity 

(including stroke) and mortality were reduced with losartan when compared to a beta blocker 

(atenolol). [165] Additionally, no difference in CV morbidity and mortality was seen with an ARB 

(valsartan) vs. a long-acting dihydropyridine calcium channel blocker (LA DHP CCB) (amlodipine) in 

patients at high risk for cardiovascular events. [166] 

The largest study supporting efficacy of an ACEI or LA DHP CCB comes from the ALLHAT trial, where over 

33,000 patients 55 years of age or older with hypertension were randomized to treatment with a 

thiazide-type diuretic (chlorthalidone), lisinopril or amlodipine. Neither the ACEI nor the LA DHP CCB 

were superior to chlorthalidone in preventing the primary endpoint of coronary heart disease or 

nonfatal MI, or all-cause mortality. For the secondary endpoints, higher rates of stroke were reported 

with the ACEI, and an increased risk of heart failure was seen with the ACEI and LA DHP CCB. [152] 
October 2014 Page 52 of 135

Other supporting evidence for a LA DHP CCB includes the Intervention as a Goal in Hypertension 

Treatment (INSIGHT) trial, where there was no difference in cardiovascular events in a group of patients 

with hypertension and one additional cardiovascular risk factor who were randomized to either long 

acting nifedipine or amiloride/HCTZ. [167] 

Patients often require multiple drugs to reduce elevated blood pressure. The systematic evidence base 

did not include studies evaluating combinations for antihypertensive drug classes. However, patients 

requiring a three drug regimen for managing hypertension should usually be on a RAS blocker, LA DHP 

CCB, and thiazide-type diuretic, before considering addition of other drug classes. Patients should not 

use combinations of two RAS blockers for the treatment of hypertension (e.g., ACEIs, ARBs, and/or 

direct renin inhibitors [DRIs]). 

Recommendation

44. We recommend against the use of more than one of the following three drug classes together

in the same patient: angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers,

or direct renin inhibitors.

Discussion

Despite the potential for additional blood pressure reduction with combination therapy of agents that 

act at the renin-angiotensin system (ACEIs, ARBs, and DRIs), data from recent clinical trials have 

reported an increased risk for harm (including hypotensive symptoms, renal dysfunction or acute kidney 

injury events, or hyperkalemia) without long-term cardiovascular or renal outcome benefit in patients 

treated with combination therapy with two or more of these three classes, compared to monotherapy. 

[164,168,169] Although these trials primarily studied high-risk patients with at least one of the following 

conditions including vascular disease, diabetes mellitus, kidney disease, or diabetic nephropathy, the 

majority of patients either had a diagnosis of hypertension or were being treated with antihypertensive 

medications. [164,168,169] 

Recommendation

45. We recommend additional therapy in refractory hypertension (for those who do not tolerate or

are not adequately controlled with triple therapy [i.e., thiazide-type diuretics, ACEI or ARB, and

LA DHP CCBs] described in Recommendation 43) or as supplementary therapy in some clinical

indications. Drug classes for consideration can include (not in priority order):

a. Aldosterone/mineralocorticoid receptor antagonists (e.g., spironolactone,

eplerenone)

b. Other potassium-sparing diuretic (i.e., amiloride)

c. Alpha adrenergic blockers

d. Beta adrenergic blockers

e. Non-dihydropyridine calcium channel blockers

f. Combined alpha-beta adrenergic blockers

g. Peripherally acting antiadrenergic agents (reserpine, pending availability)

h. Direct acting vasodilators (e.g., hydralazine, minoxidil)

i. Centrally acting antiadrenergic drugs (e.g., clonidine, methyldopa)
October 2014 Page 53 of 135

Discussion

Antihypertensive agents other than thiazide-type diuretics, ACEIs, ARBs, and LA DHP CCBs have a role in 

certain situations. Adequate treatment of high blood pressure to recommended goals frequently 

requires use of multiple antihypertensive agents. The alternative drugs are often used fourth- or fifthline as add-on therapy when combination therapy with the preferred antihypertensive drug classes has 

failed to adequately control blood pressure, or in cases where there is intolerance to or 

contraindications to the preferred drug classes. Several of these drugs were used as add-on therapy in 

the pivotal randomized controlled trials used in the systematic evidence base.

Overall, there was a lack of studies in the evidence base to provide specific recommendations for many 

of the drug classes listed above (e.g., combined alpha-beta adrenergic blockers, and centrally acting 

antiadrenergic drugs). Consideration should be given to the presence of comorbid conditions, risk of 

adverse events with a particular drug class, and the patient’s willingness to adhere to multi-drug 

regimens. 

Refer to other VA/DoD Clinical Practice Guidelines for treatment recommendations in patients with 

hypertension and chronic heart failure6

, CKD7 (see also Recommendation 47), or ischemic heart 

disease8

. General comments and available outcomes based on the evidence are included below for 

some of the drug classes. 

• Aldosterone/mineralocorticoid receptor antagonists: Spironolactone is often added on to

multi-drug regimens in patients with resistant hypertension, and for hyperaldosteronism.

Eplerenone is an alternative for patients experiencing antiandrogen adverse effects with

spironolactone.

• Other potassium sparing diuretics (i.e. amiloride): Amiloride is frequently combined with a

thiazide-type diuretic (e.g., HCTZ) in patients with hypertension, due to its benefit of preserving

potassium. In the INSIGHT trial, amiloride/HCTZ and nifedipine produced comparable results in

reducing CV morbidity, and amiloride/HCTZ was significantly more effective in reducing HF.

[167] Amiloride is also often added to a multidrug regimen in resistant hypertension when

spironolactone is not tolerated or contraindicated.

• Beta blockers: Evidence for a clear benefit of beta blockers in reducing cardiovascular events is

mixed. For the outcomes of CV morbidity and mortality, a beta blocker (atenolol) was inferior to

ARB (losartan). [165] However, no difference was noted between propranolol and the thiazide

bendrofluazide for all CV events, coronary events and all-cause death, with the exception of a

lower stroke rate with the thiazide. [129] Other important indications for beta blockers

6 See the VA/DoD Clinical Practice Guideline for the Management of Chronic Heart Failure. Available at: 

http://www.healthquality.va.gov/guidelines/cd/chf/index.asp 7 See the VA/DoD Clinical Practice Guideline for the Management of Chronic Kidney Disease. Available at: 

http://www.healthquality.va.gov/guidelines/cd/ckd/index.asp 8 See the VA/DoD Clinical Practice Guideline for the Management of Ischemic Heart Disease. Available at: 

http://www.healthquality.va.gov/guidelines/cd/ihd/index.asp 
October 2014 Page 54 of 135

unrelated to hypertension include hypertensive patients with underlying coronary artery 

disease, following MI, and in low ejection-fraction heart failure. Beta blockers may be an 

alternative therapy in patients with contraindications or intolerance to an ACEI or ARB. The 

adverse event profile of beta blockers may limit their use.

• Non-dihydropyridine calcium channel blockers: Evidence supporting use of a non-DHP CCB

comes from one large trial which reported no difference in CV endpoints (all-cause mortality,

nonfatal stroke, MI) when verapamil SR (with ACEI) was compared with beta blocker (with HCTZ)

in hypertensive patients with CAD. [170] A non-DHP CCB can be considered in hypertensive

patients with atrial fibrillation when beta blockers are not tolerated.

• Reserpine (pending availability): Reserpine, if available, can also be used as supplemental

therapy. In ALLHAT, reserpine, atenolol or clonidine were the options for step two drugs. [171]

Reserpine combined with HCTZ and hydralazine was the active treatment arm in the Veterans

Administration Cooperative Study Group on Antihypertensive Agents morbidity trial. [118]

Limitations to the use of reserpine include adverse events and availability. As of August 2014,

there are no commercially available reserpine products, due to a shortage of raw material. [172]

Recommendation

46. We recommend against the use of alpha-adrenergic blockers as monotherapy, but this class of

agents may be used as supplemental therapy or if warranted by comorbid conditions (e.g.,

symptomatic prostatic hypertrophy). (Modified from 2004 VA/DoD HTN CPG)

Discussion

The evidence for this recommendation comes from the initial findings of the ALLHAT study. [171] The 

ALLHAT study was a randomized, double-blind, multicenter clinical trial sponsored by the NHLBI. It was 

designed to determine whether the occurrence of fatal coronary heart disease or nonfatal MI was lower 

for high-risk patients with hypertension treated with a CCB (represented by amlodipine), an ACEI 

(represented by lisinopril), or an alpha blocker (represented by doxazosin), each compared with diuretic 

treatment (represented by chlorthalidone). Chlorthalidone was found to be superior to doxazosin, 

leading to early termination of the doxazosin arm of the trial. In high-risk hypertensive patients, 

chlorthalidone significantly reduced the risk of total CVD events, particularly heart failure, compared 

with doxazosin. Furthermore, the doxazosin arm compared with the chlorthalidone arm had a higher 

risk of stroke and total CVD events. [154] The study population of interest was 55 years of age and older.

Specific Populations

Patients with Chronic Kidney Disease

Recommendation

47. In patients with hypertension and chronic kidney disease (reduced kidney function with

albuminuria), we recommend treatment with an angiotensin-converting-enzyme inhibitor, or

angiotensin II receptor blocker for improving kidney outcomes. (Modified from 2004 VA/DoD

HTN CPG)
October 2014 Page 55 of 135

Discussion 

The recommendation for selection of antihypertensive therapy in patients with CKD is based on the 

beneficial effect on kidney outcomes, as clinical trials in patients with CKD either did not evaluate 

cardiovascular endpoints as a primary outcome, or found no difference between treatment groups for 

cardiovascular outcomes evaluated as secondary endpoints or by subgroup analyses. [173-176] 

The recommendation to use an ACEI or ARB as initial therapy in patients with hypertension and CKD 

with albuminuria is based on the beneficial effects on kidney outcomes, with evidence as outlined in the 

VA/DoD Clinical Practice Guideline on the Management of CKD.9 The majority of data reviewed shows 

that treatment with an ACEI in patients with non-diabetic kidney disease slows the progression of CKD; 

with evidence for use of an ARB in this patient population based on limited data on surrogate outcomes. 

The ACEIs have also been shown to decrease the progression of kidney disease and reduce the 

combined risk of death, dialysis, or transplantation in patients with type 1 diabetes mellitus and 

albuminuria. [177] In patients with type 2 diabetes mellitus and albuminuria, treatment with an ACEI or 

an ARB decreased the progression of kidney disease. In two long-term trials in patients with 

nephropathy due to type 2 diabetes, the primary endpoint of composite all-cause mortality, doubling of 

serum creatinine, and end stage renal disease (ESRD) was significantly reduced with an ARB compared 

to placebo [173,178] or treatment with a DHP CCB. [173] When treatment with an ACEI was compared 

to an ARB in patients with type 2 diabetes and nephropathy, an ARB was not inferior to treatment with 

an ACEI for the primary endpoint of change in glomular filtration rate (GFR); and the secondary 

endpoints of annual change in GFR, level of serum creatinine, urinary albumin excretion rate, and blood 

pressure were not significantly different between treatment groups. [179] 

The evidence review for this guideline is in agreement with the VA/DoD CKD guideline to use an ACEI or 

ARB in patients with hypertension and CKD with proteinuria. The clinical trials evaluating treatment 

comparisons found that an ACEI improved kidney outcomes compared to treatment with a DHP CCB, 

[180-183] as did treatment with an ARB compared to a DHP CCB. [173] 

It is recommended that in patients with CKD, if either an ACEI or ARB is not tolerated, the other class 

should be used. As discussed in the VA/DoD CKD guideline,9 use of an ACEI or ARB is commonly 

associated with an increase in serum creatinine and potassium. Patients with CKD prescribed an ACEI or 

ARB should be monitored closely for changes in electrolytes and kidney function, with dose 

adjustments, or modifications in treatment, as indicated. Potassium-sparing diuretics should be used 

with caution in patients with CKD, and may contribute to hyperkalemia if prescribed with an ACEI or 

ARB, or in patients with other risk factors for hyperkalemia. In one evaluation of patients with resistant 

hypertension being considered for treatment with spironolactone, predictors of hyperkalemia included 

an eGFR <45 ml/min/1.73m2 in patients with a potassium >4.5 mEq/L. [184] Patients experiencing cough 

on an ACEI should be switched to an ARB. [185-187] An ARB should be used with caution in patients who 

have previously experienced angioedema with an ACEI. [188,189]

9 See the VA/DoD Clinical Practice Guideline for the Management of Chronic Kidney Disease. Available at: 

http://www.healthquality.va.gov/guidelines/cd/ckd/index.asp
October 2014 Page 56 of 135

Add-on Antihypertensive Therapy 

Most patients with CKD and hypertension will require more than one medication to achieve the 

recommended blood pressure target. [173,179-182] In the trials reviewed, the most frequently used 

add-on therapy to an ACEI or ARB was a diuretic, followed by a LA DHP CCB or beta blocker. A diuretic 

should be considered as add-on or concomitant initial therapy with an ACEI or ARB in patients with CKD, 

as a general recommendation to improve cardiovascular outcomes in patients with hypertension. It is 

generally recommended that thiazide-type diuretics be used if eGFR >30 ml/min/1.73 m2

, with loop 

diuretics added to or instead of thiazide-type diuretics for patients with more advanced kidney disease. 

[190-192] A LA DHP CCB may also be considered as add-on therapy as per a subgroup analysis of the 

ACCOMPLISH trial, [151] where a decrease in progression of CKD (doubling serum creatinine or ESRD) 

and combined cardiovascular events and CKD events were reported in patients receiving combination 

with an ACEI (benazepril) and LA DHP CCB (amlodipine) compared to treatment with benazepril and a 

thiazide-type diuretic (HCTZ), although the thiazide-type diuretic was dosed lower than what had been 

proven effective in CVD outcome trials. [193] Drug therapy selection should also take into account 

patient comorbidities and tolerability.10

Patients with a history of stroke

There is no evidence that the choice of drug should differ in patients with a history of stroke. In poststroke patients, the addition of an ACEI may be considered, but should be paired with a diuretic. An ACEI 

may provide additional benefit to existing antihypertensive therapies or for patients who are not 

hypertensive for primary stroke protection. In the Perindopril pROtection aGainst REcurrent Stroke 

Study (PROGRESS) trial, the thiazide-type diuretic indapamide, when added on to ACEI therapy with 

perindopril, resulted in lower rates of CV morbidity and mortality, and stroke, over that seen with ACEI 

alone in patients with a history of TIA or minor stroke. There were no blood pressure entry criteria, 

although it was recommended that individuals with uncontrolled hypertension receive antihypertensive 

therapy with agents other than ACEIs before entry to the trial. [194] 

African American Population

Recommendations 

48. In African American patients with hypertension, we recommend against using an angiotensinconverting-enzyme inhibitor or angiotensin II receptor blocker as monotherapy.

49. In African American patients with hypertension and stage 1-3 chronic kidney disease, we

suggest a combination of a thiazide-type diuretic (for cardiovascular protection) with either an

angiotensin-converting-enzyme inhibitor or angiotensin II receptor blocker (for renal

protection).

Discussion

Thiazide-type diuretics remain the drugs of choice in initial therapy for African Americans with 

hypertension. [195] The ALLHAT study included more than 15,000 African Americans and found that the 

10 See the VA/DoD Clinical Practice Guideline for the Management of Chronic Kidney Disease. Available at: 

http://www.healthquality.va.gov/guidelines/cd/ckd/index.asp
October 2014 Page 57 of 135

ACEI (lisinopril) was less effective in lowering blood pressure than the thiazide-type diuretic 

(chlorthalidone) or the LA DHP CCB (amlodipine). [195] The study population of interest was 55 years of 

age and older. The study found that those participants randomized to the ACEI (lisinopril) versus the 

thiazide-type diuretic (chlorthalidone) were at a 40% greater risk of stroke, 32% greater risk of heart 

failure, and 19% great risk of CVD. [152] There was no difference in major CVD outcomes between the 

thiazide-type diuretic and the LA DHP CCB, besides higher incidence of heart failure with the CCB. The 

ALLHAT study also found that African Americans randomized to the LA DHP CCB (amlodipine) had a 

greater adherence to the treatment and ended up needing fewer medications to reach the blood 

pressure goal than those randomly assigned to ACEI (lisinopril). [196] Additionally, the Losartan 

Intervention For Endpoint reduction in hypertension study (LIFE) reported that African Americans on a 

beta-blocker (atenolol) had better cardiovascular outcomes than those on an ARB (losartan). [197] 

Furthermore, in the African American Study of Kidney Disease and Hypertension (AASK), ACEIs were 

found to be more effective than beta blockers or LA DHP CCBs in slowing GFR decline among African 

American patients with proteinuria. [183] The AASK trial would suggest that African Americans with CKD

should be placed on an ACEI, but the ALLHAT study reported that chlorthalidone was superior to 

lisinopril for CVD outcomes in African Americans. [176] Therefore for African American patients with 

CKD on monotherapy with an ACEI or an ARB, a thiazide-type diuretic should be added to augment the 

cardiovascular protection of diuretics to the renal protection of ACEIs or ARBs. 

Women of reproductive age 

The treatment of hypertension in women who have the potential to become pregnant requires special 

consideration due to potential adverse effects to a fetus. Women of reproductive age with hypertension 

should be counseled about the potential teratogenic effects of their medications. In addition, women 

should be counseled to alert their providers whenever they are planning to become, or realize that they 

already are, pregnant. Medications which act through the renin-angiotensin system (i.e., ACEIs and 

ARBs) should be avoided during pregnancy since they can lead to renal dysgenesis, pulmonary 

hypoplasia, intrauterine growth restriction, or death of the fetus. [198-203] Direct renin inhibitors may 

carry a similar risk and should also be avoided. Spironolactone and RAS blockers should be avoided in 

women of child-bearing potential due to their anti-androgenic effects during fetal development and 

concern for undervirilization of a male fetus. Providers should enter a discussion with women about 

their plans for pregnancy or birth control prior to the initiation of medications for the treatment of 

hypertension. For patients who are interested in becoming pregnant, or who are not on reliable birth 

control and at risk for pregnancy, alternative agents should be utilized such as labetalol, calcium channel 

blockers, or thiazide-like diuretics. Elevated blood pressure during pregnancy can be caused by a myriad 

of conditions such as acute illness, chronic hypertension, pregnancy in hypertension, or pre-eclampsia 

and should be managed by a provider with experience in caring for these conditions, such as an 

obstetrician. 
October 2014 Page 58 of 135 

Deployed Service Members: Considerations for treatment of hypertension in a deployed 

environment

Medical support 

Deployed Service Members are instructed to seek healthcare on their Forward Operating Base 

(FOB)/Combined Operating Base (COB) while in a Theater of Operations. If more urgent care is required, 

Service Members are then air evacuated to a higher level of care. Routine healthcare for Service 

Members while deployed in a Theater of Operations may vary from a single provider and medic at a 

Battalion Aid Station (BAS) on a remote FOB, to a Troop Medical Clinic (TMC), or forward surgical team 

(FST) or Combat Support Hospital (CSH) on a COB. The ability to have routine basic labs drawn, such as 

blood chemistry or complete blood count (CBC), is found at CSHs and FSTs. 

Harsh environmental conditions

It is not unusual for Service Members to be working outdoors (sun and/or shade) for an extensive time 

in temperatures greater than 120° F, and/or at altitudes greater than 5000 feet. Fluid loss due to work 

intensity, duration of heat exposure, and clothing/equipment worn, as well as medications taken, may 

also result in increased dehydration rates. Additionally, in these cases acclimatization to heat and/or 

altitude may cause additional fluid loss. Service Members who are deployed and have a preexisting 

diagnosis of hypertension may become prone to dehydration in austere/extreme climates as they 

engage in extreme physical activity. If not contraindicated, primary care providers should consider 

prescribing DHP CCBs, ACEIs or ARBs as the preferred antihypertensive. However, for patients who are 

newly diagnosed with hypertension while in a deployed environment, the primary care providers should 

consider using DHP CCBs as the preferred agents. These medications are available in once a day 

formulations, do not limit heart rate, and do not require electrolytes to be checked after initiation. 

Moreover, Service Members may also be deployed to cold weather environments and will also 

experience diuresis as part of their acclimatization process. Clinicians who care for Service Members 

who are in a deployable status should be cognizant of the Service Member’s worldwide mission, and 

remember to ask the patient if and where they will be deploying. This will facilitate modifying the 

patient’s current medications, if necessary, so as to diminish any serious side effects that may affect 

electrolyte balance because of the limited ability to monitor the patient. Moreover, providers should 

also be aware that certain antihypertensive medications (e.g., beta-blockers or non-DHP CCBs) may limit 

maximum heart rate. As many Service Members are involved in physically demanding work, limiting 

their ability to increase cardiovascular output may increase their risk of environmental injury and 

compromise their ability to respond to a tactical situation that requires running, jumping, carrying heavy

objects, or other types of sustained heavy physical exertion. Additionally, primary care managers should

be mindful of the varying formulations of medications. For example, gel caps can melt and should not be 

used in hot climates. 

Nuclear, biological, and chemical (NBC) operations 

In high operational tempo environments, Service Members may be operating in chemical 

protective/flame protective over garments and equipment, sometimes for several hours at a time (e.g., 

fire fighters, decontamination teams). The donning of chemical/fire resistant protective over garments 

dramatically increases the Service Member’s heat load, in addition to the austere environmental 

conditions. Moreover, it is also more difficult to drink fluids, eat, or take oral medications while wearing 
October 2014 Page 59 of 135

a protective mask. Depending on the tactical situation, Service Members may also be required to take 

medications for pretreatment against nerve agent poisoning (pyridostigmine bromide) or biological 

warfare agents (usually a fluoroquinolone). If a Service Member is exposed to a nerve agent, he or she 

will be treated intramuscularly with Atropine and 2-PAM Chloride. Clinicians who care for deployed 

members should also be cautious about any medication that would either decrease the Service 

Members ability to compensate for heat stress, make them more sensitive to nerve agent poisoning, or 

make resuscitation medication drugs less effective (if indicated). 

Adherence 

Operational tempo in a deployed environment is high-paced. If at all possible, clinicians should attempt 

to prescribe daily dosing of chronic medications to facilitate medication adherence in deployed Service 

Members. Likewise, meals are either frequently carried by the Service Member or are available only at 

irregular intervals. Thus, if possible, the provider should avoid/limit prescribing medications that must 

be taken with food or that are required to be added to food or beverages. 

Nutrition

Service Members frequently do not get a choice regarding where they are going, what they are doing, or 

where they will eat in a deployed/training environment. Food sources may range from Meals Ready to 

Eat (MREs), items received in care packages, to training area or FOB/COB dining facilities. Depending 

upon what area of responsibility the Service Member is deployed to/training in, these rations may be 

high in sodium and fat. These nutritional factors may impact hypertension management and necessitate 

provider counseling related to diet.
October 2014 Page 60 of 135

Appendix A: Evidence Review Methodology

The Clinical Practice Guideline Champions were tasked with identifying key evidence questions to guide 

the systematic review of the literature on hypertension. These questions, which were developed in 

consultation with the Lewin team, addressed clinical topics of the highest priority for the Veterans 

Affairs and Department of Defense populations. The key questions follow the population, intervention, 

comparison, outcome, timing and setting (PICOTS) framework for evidence questions, as established by 

the Agency for Healthcare Research and Quality (AHRQ). Table A-1 provides a brief overview of the 

PICOTS typology.

Table A-1. PICOTS [204]

P

Patients, 

Population 

or Problem

A description of the patients of interest. It includes the condition(s), populations 

or sub-populations, disease severity or stage, co-morbidities, and other patient 

characteristics or demographics.

I Intervention 

or Exposure

Refers to the specific treatments or approaches used with the patient or 

population. It includes doses, frequency, methods of administering treatments, 

etc.

C Comparison

Describes the interventions or care that is being compared with the 

intervention(s) of interest described above. It includes alternatives such as 

placebo, drugs, surgery, lifestyle changes, standard of care, etc.

O Outcome

Describes the specific results of interest. Outcomes can include short, 

intermediate, and long-term outcomes, or specific results such as quality of life, 

complications, mortality, morbidity, etc.

(T) Timing, if 

applicable

Describes the duration of time that is of interest for the particular patient 

intervention and outcome, benefit, or harm to occur (or not occur).

(S) Setting, of 

applicable

Describes the setting or context of interest. Setting can be a location (such as 

primary, specialty, or inpatient care).

The Champions and evidence review team carried out several iterations of this process, each time 

narrowing the scope of the CPG and the literature review by prioritizing the topics of interest. Table A-2 

contains the final set of key questions (KQs) used to guide the systematic review for this CPG. 

Conducting the Systematic Review

The methods guiding this systematic review are described below. In part, these methods follow the 

guidelines for conducting a systematic review set forth by AHRQ in the Methods Guide for Effectiveness 

and Comparative Effectiveness Reviews. [205] The methods also follow the guidance set forth by the 

VA/DoD in the Guideline for Guidelines document. [10] 

The Lewin Group conducted a systematic review in support of this VA/DoD CPG. The target population 

considered in the systematic review was outpatient adults ages 18 years or older. The systematic review 

did not address pregnant women, peri-operative/inpatient adults, children or adolescent populations. 
October 2014 Page 61 of 135

The review addressed various management strategies for patients with HTN. This included assessing the 

benefits and harms associated with antihypertensive pharmacologic therapies as well as the blood 

pressure thresholds to initiate therapy and appropriate blood pressure targets. In addition to physiciandirected management strategies, the review assessed the impact of non-pharmacologic therapies (e.g., 

weight reduction, sodium reduction, physical activity) in reducing HTN. The review also evaluated what 

measurement techniques are the best indicators to initiate anti-hypertensive therapy. The target 

audience of the systematic review and CPG are VA/DoD and other primary care physicians and 

specialists who treat active and inactive military personnel.

Extensive literature searches identified 19,888 potentially relevant studies. Of those, 19,093 were 

excluded upon title and abstract review for not meeting the inclusion and exclusion criteria. A total of 

799 full-text articles were reviewed of which an additional 649 articles were excluded. Articles excluded 

from the evidence base for a particular key question were removed for one or more of the following 

reasons: the article was published before 1966, the article was not in English, the study type did not 

qualify, the study population was not a relevant population of interest, the intervention was not 

relevant, the comparator was not relevant, the outcomes examined were not relevant, the study setting 

was not relevant, the sample size was <100, or the study follow-up period was less than one year. 

Overall, 150 publications addressed one or more of the KQs and comprised the evidence base for this 

literature review. Table A-2 indicates the number of studies that addressed each of the questions. Figure 

A-1 displays a summary of the phases of the systematic review. 

Table A-2. Evidence Base for Included Studies by Key Question

Number Question Number and type 

of included studies

1 In adult outpatients, at what systolic blood pressure threshold does 

initiating pharmacologic therapy for hypertension result in clinically 

improved outcomes?

Does it differ based on the patient’s age, gender, race, or history of 

prior stroke, LVH, diabetes, CKD (with and without proteinuria), CHF, 

CAD or combined CVD disease?

13 RCTs

2 In adult outpatients, at what diastolic blood pressure threshold does 

initiating pharmacologic therapy for hypertension result in clinically 

improved outcomes?

Does it differ based on the patient’s age, gender, race, or history of 

prior stroke, LVH, diabetes, CKD (with and without proteinuria), CHF, 

CAD or combined CVD disease?

12 RCTs

3 For adult outpatients being treated for hypertension, what is the 

systolic blood pressure goal that is associated with improved health 

outcomes?

Does it differ based on the patient’s age, gender, race, or history of 

prior stroke, LVH, diabetes, CKD (with and without proteinuria), CHF, 

21 RCTs
October 2014 Page 62 of 135

Number Question Number and type 

of included studies

CAD or combined CVD disease?

4 For adult outpatients being treated for hypertension, what is the 

diastolic blood pressure goal that is associated with improved health 

outcomes?

Does it differ based on the patient’s age, gender, race, or history of 

prior stroke, LVH, diabetes, CKD (with and without proteinuria), CHF, 

CAD or combined CVD disease?

17 RCTs

5 In adult outpatients with an abnormal BP measurement, which 

measurement technique is the best indicator of whether 

hypertension therapy should be initiated and is more predictive of 

LVH, CKD, CVD, and end organ damage?

• Office versus Home

• Office versus 24 hour ambulatory blood pressure monitor

• 24 hour ambulatory blood pressure monitor versus Home

Does it differ based on the patient’s age, gender, race, or history of 

prior stroke, LVH, diabetes, CKD (with and without proteinuria), CHF, 

CAD or combined CVD disease?

7 Observational 

Studies

6 In adult outpatients, how effective is non-pharmacologic therapy in reducing BP?

a. Weight reduction? 11 RCTs

b. Reduced alcohol consumption? 1 RCT

c. Sodium reduction? 2 RCTs

d. Exercise/physical activity

• Are certain types of exercise more effective?

6 RCTs

e. Dietary and non-dietary potassium? 0 RCTs

f. Combined dietary modification (two or more dietary

changes)?

6 RCTs

g. Mind-body therapy/behavioral therapy? 4 RCTs

h. Improved adherence to treatment through self-monitoring,

education interventions (patient and/or provider) and case

management?

30 RCTs

7 In adults with hypertension on pharmacotherapy, what is the 

evidence that improved health outcomes vary by drug, within drug 

classes, or by drug class?

56 RCTs

8 In healthy adults with hypertension and no comorbidities, what is 2 RCTs
October 2014 Page 63 of 135

Number Question Number and type 

of included studies

the evidence that initiation of pharmacotherapy as monotherapy, 

sequential therapy, or combination therapy (>2 drugs) produces the 

best results in improved blood pressure control, length of time to 

reach blood pressure goal, or health outcomes?

9 In adults with hypertension, what is the evidence that there is a 

difference between thiazide-type diuretics for morbidity, mortality, 

or blood pressure reduction?

8 RCTs

a. For each of these thiazide-type diuretics, how does the dose

relate to the outcomes?

7 RCTs, 1 SR/MA

Figure A-1. Systematic Review Flow Diagram

Records identified through multiple databases 

(duplicates removed at time of search)

(n =19,888) 

Records screened

(n =19,888) 

Records excluded

(n =19,093) 

Full-text articles assessed for eligibility

(n =799) 

Full-text articles excluded, with 

reason code

(n =595) 

Studies included in qualitative 

synthesis

(n =204) 
October 2014 Page 64 of 135

Inclusion and Exclusion Criteria

To guide the collection of evidence, the team developed an initial set of inclusion and exclusion criteria 

that was discussed and agreed upon by the CPG Champions. While there are some overarching criteria 

for the review, the team also established individual sets of inclusion and exclusion criteria for each of 

the key questions, as necessary. 

In some cases, the inclusion and exclusion criteria were influenced by recently published systematic 

evidence reviews or other publications. The utilization of previous publications as a starting point to 

address all or some of the key questions allowed the current literature search to be more efficient and 

effective. 

Figure A-2 presents the overarching criteria that were applied to the literature searches and to the 

review of resulting literature identified through these searches. 

A “best available evidence” approach was implemented to sort the evidence for the systematic review. 

[206] To be included in the systematic review, a study must be a prospective, randomized or 

nonrandomized (observational) controlled trial with an independent, concurrent control group. If no 

high quality intervention trials are available to address a particular key question, relevant observational 

studies were identified and included in the systematic review.

Figure A-2. General Inclusion and Exclusion Criteria

Outcomes

The patient outcomes of interest considered during the literature review for this CPG included:

• Blood pressure control

• Mortality: cardiovascular and all-cause

• Stroke: fatal and non-fatal

• CHF

• CAD, including MI and revascularization during an acute coronary syndrome

• Aortic events (e.g., aneurysm rupturing)

• Studies that enrolled adults (≥18 years) will be included. In studies with mixed adult and children

populations, we will require that at least 85 percent of the enrolled patients are greater than

age 18.

• Studies must be published in English.

• Publication must be a full clinical study or systematic review; abstracts alone will not be

included. Similarly, letters, editorials, and other publications that are not full-length, clinical

studies will not be included.

• Only human studies will be included.

• Studies that study acute hypertension/emergency treatment of hypertension will be excluded.

• Studies that look at only pulmonary hypertension will be excluded. If the study looks at regular

and pulmonary hypertension, it will be included.

• Studies that look at pediatric hypertension will be excluded.
October 2014 Page 65 of 135

• LVH

• CKD: progression to ESRD, starting dialysis, kidney transplant, doubling of serum creatinine or

reduction of GFR by 50%

Literature Search Strategies 

Detailed search logic reflecting the PICOTS of interest were developed for each key question and used to 

identify relevant randomized controlled trials and other study design types as needed. The literature 

searches were conducted using the following bibliographic and other databases: PubMed/MEDLINE, 

EMBASE, and the Cochrane databases, including Cochrane Central Register of Controlled Trials 

(CENTRAL), Cochrane Database of Systematic Reviews (CDSR) and Database of Abstracts of Reviews of 

Effects (DARE). The CPG Champions also contributed articles as part of the evidence generation step. 

The literature search strategies incorporated key text terms identified from an initial review of relevant 

systematic reviews and primary research studies on related topics (including how they are indexed in 

their respective databases, e.g., use of medical subject headings [MeSH] in PubMed, EMTREE terms in 

EMBASE) and any terms identified by the CPG Champions or members of the evidence review team, 

including a clinical and research expert on the subject matter. Members of the evidence review team 

including a librarian, as needed, reviewed the search strategies developed to ensure 

comprehensiveness. Duplicates of studies were discarded during the search process so that each 

publication is represented only once in the resulting evidence base for each key question. 

The search strategies employed combinations of free-text keywords as well as controlled vocabulary 

terms including (but not limited to) MeSH and EMTREE terms. Search sets were structured to address 

specific key questions and sub-questions. The strategies for PubMed are presented first, followed by the 

search strategies used in EMBASE and in Cochrane, including CENTRAL, CDSR and DARE. Searches of 

EMBASE and Cochrane were conducted in parallel with searches in PubMed.

For PubMed, two searches strategies were constructed for each key question. The first retrieved studies 

that are indexed in PubMed, and the second strategy captured any relevant studies which were in the 

process of being indexed or had not yet been indexed. 

Key Questions 1 and 2

Date parameters ranged from 1966 to present in order to include seminal literature published in the late 

1960s. We utilized the evidence base from a systematic review, Law et al., [207] which covered the 

years 1966-2007 and then conducted our own search from 2007 to present.

PubMed 

1. Indexed Studies

Concept(s) Search Statement

#1

Blood pressure, 

hypertension, 

prehypertension

Blood Pressure[mh]/drug effects OR Hypertension[mh]/drug therapy OR 

Prehypertension[mh] OR Systole[mh] OR Diastole[mh] OR (hypertensive[tiab] OR 

prehypertensive[tiab] OR systolic pressure*[tiab] OR diastolic pressure*[tiab] OR 

arterial pressure*[tiab]) OR BP[tiab] OR ((systol* OR diastol*) AND (pressure* OR 

mmHg OR mmHg)) OR (70 mmHg[tiab] OR 80 mmHg[tiab] OR 90 mmHg[tiab] OR 100 

mmHg[tiab] OR 110 mmHg[tiab] OR 120*mmHg[tiab] OR 130*mmHg[tiab] OR 

140*mmHg[tiab] OR 150*mmHg[tiab] OR 160*mmHg[tiab] OR 170*mmHg[tiab] OR 
October 2014 Page 66 of 135

Concept(s) Search Statement

180*mmHg[tiab]) 

#2 Outcomes of interest

(Mortality[mh] OR mortality[tiab] OR Death[mh] OR death*[tiab] OR Morbidity[mh] 

OR morbidity[tiab] OR Cause of Death[mh] OR Fatal Outcome[mh]) OR 

(Cardiovascular Diseases/prevention[mh] OR Cardiovascular 

Diseases/epidemiology[mh] OR Cardiovascular Diseases/etiology[mh] OR 

Cardiovascular Diseases/physiopathology[mh] OR Coronary Disease/prevention[mh] 

OR Coronary Disease/epidemiology[mh] AND Coronary Disease/etiology[mh] OR 

Coronary Disease/physiopathology[mh] OR Coronary Artery Disease/prevention[mh] 

OR Coronary Artery Disease/epidemiology[mh] OR Coronary Artery 

Disease/etiology[mh] OR Coronary Artery Disease/physiopathology[mh] OR 

Myocardial Infarction/prevention[mh] OR Myocardial Infarction/epidemiology[mh] 

OR Myocardial Infarction/etiology[mh] OR Myocardial 

Infarction/physiopathology[mh] OR Heart Failure/prevention[mh] OR Heart 

Failure/epidemiology[mh] OR Heart Failure/etiology[mh] OR Heart 

Failure/physiopathology[mh] OR Cerebrovascular Disorders/prevention[mh] OR 

Cerebrovascular Disorders/epidemiology[mh] OR Cerebrovascular 

Disorders/etiology[mh] OR Cerebrovascular Disorders/physiopathology[mh] OR 

Stroke/prevention[mh] OR Stroke/epidemiology[mh] OR Stroke/etiology[mh] OR 

Stroke/physiopathology[mh] OR Kidney/epidemiology[mh] OR Kidney/etiology[mh] 

OR Kidney/physiopathology[mh]) OR (myocardial infarction[tiab] OR heart 

failure[tiab] OR stroke[tiab] OR cerebrovascular disorder*[tiab] OR cerebrovascular 

event*[tiab] OR kidney failure[tiab] OR chronic kidney disease*[tiab] OR CKD[tiab]) 

OR (Myocardial Revascularization[mh] OR Myocardial Revascularization[tiab]) OR 

(Creatinine[mh] OR Creatinine[tiab]) OR (Glomerular Filtration Rate[mh] OR 

Glomerular Filtration Rate[tiab] OR GFR[tiab] OR eGFR[tiab] OR estGFR[tiab]) OR 

(hospitalization[tiab] OR coronary revascularization[tiab] OR angioplasty[tiab] OR 

stent*[tiab] OR peripheral revascularization[tiab] OR carotid[tiab] OR extremity 

revascularization[tiab] OR end stage renal disease[tiab] OR ESRD[tiab]) OR 

((aggressive therapy[tiab] AND (goal*[tiab] OR target*[tiab]) AND (mmHg[tiab] OR 

mmHg[tiab])) OR morbidity[tiab])

#3 Antihypertensive 

treatment

Antihypertensive Agents/therapeutic use[mh] OR Hypertension/drug therapy[mh] OR 

((antihypertensive OR anti-hypertensive) AND (drug therapy OR drug treatment)) OR 

(pharmacologic therapy OR pharmacologic lowering of blood pressure)

#4 Combine #1 AND #2 AND #3

#5 Limit to RCTs #4 AND Randomized Controlled Trial[PT]

#6

Apply date and 

language limit to 

RCTs

#5 AND ("1966/01/01"[PDAT] : "2013/12/16"[PDAT]) AND English[lang] 

2. Indexed Studies for CKD Patients only

Concept(s) Search Statement

#1

Blood pressure, 

hypertension, 

prehypertension

Blood Pressure[mh]/drug effects OR Hypertension[mh]/drug therapy OR 

Prehypertension[mh] OR Systole[mh] OR Diastole[mh] OR (hypertensive[tiab] OR 

prehypertensive[tiab] OR systolic pressure*[tiab] OR diastolic pressure*[tiab] OR arterial 

pressure*[tiab]) OR BP[tiab] OR ((systol* OR diastol*) AND (pressure* OR mmHg OR 

mmHg)) OR (70 mmHg[tiab] OR 80 mmHg[tiab] OR 90 mmHg[tiab] OR 100 mmHg[tiab] OR 

110 mmHg[tiab] OR 120*mmHg[tiab] OR 130*mmHg[tiab] OR 140*mmHg[tiab] OR 

150*mmHg[tiab] OR 160*mmHg[tiab] OR 170*mmHg[tiab] OR 180*mmHg[tiab]) 

#2 CKD population renal insufficiency, chronic[majr] OR kidney failure, chronic[majr]

#3 Limit to RCTs randomized controlled trial[pt]

#4 Combine #1 AND #2 AND #3
October 2014 Page 67 of 135

#4 Apply date and 

language limit #4 AND (#5 AND ("1966/01/01"[PDAT] : "2013/12/16"[PDAT]) AND English[lang] 

3. Non-indexed Studies

Concept(s) Search Statement

#1

Blood pressure, 

hypertension, 

prehypertension

Blood Pressure[tiab] OR Prehypertension[tiab] OR Systole[tiab] OR Diastole[tiab] OR 

(hypertensive[tiab] OR prehypertensive[tiab] OR systolic pressure*[tiab] OR diastolic 

pressure*[tiab] OR arterial pressure*[tiab]) OR BP[tiab] OR ((systol* OR diastol*) AND

(pressure* OR mmHg OR mmHg)) OR (70 mmHg[tiab] OR 80 mmHg[tiab] OR 90 

mmHg[tiab] OR 100 mmHg[tiab] OR 110 mmHg[tiab] OR 120*mmHg[tiab] OR 

130*mmHg[tiab] OR 140*mmHg[tiab] OR 150*mmHg[tiab] OR 160*mmHg[tiab] OR 

170*mmHg[tiab] OR 180*mmHg[tiab]) 

#2 Outcomes of 

interest

(Mortality[tiab] OR death*[tiab] OR morbidity[tiab] OR Cause of Death[tiab] OR Fatal 

Outcome[tiab]) OR (Cardiovascular Diseases [tiab] OR Coronary Disease [tiab] OR 

Coronary Artery Disease[tiab]) OR (myocardial infarction[tiab] OR heart failure[tiab] OR 

stroke[tiab] OR cerebrovascular disorder*[tiab] OR cerebrovascular event*[tiab] OR 

kidney failure[tiab] OR chronic kidney disease*[tiab] OR CKD[tiab]) OR Myocardial 

Revascularization[tiab] OR Creatinine[tiab] OR (Glomerular Filtration Rate[tiab] OR 

GFR[tiab] OR eGFR[tiab] OR estGFR[tiab]) OR (hospitalization[tiab] OR coronary 

revascularization[tiab] OR angioplasty[tiab] OR stent*[tiab] OR peripheral 

revascularization[tiab] OR carotid[tiab] OR extremity revascularization[tiab] OR end stage

renal disease[tiab] OR ESRD[tiab]) OR ((aggressive therapy[tiab] AND (goal*[tiab] OR 

target*[tiab]) AND (mmHg[tiab] OR mmHg[tiab])) OR morbidity[tiab])

#3 Antihypertensive 

Treatment

Antihypertensive Agents[tiab] OR ((antihypertensive OR anti-hypertensive) AND (drug 

therapy OR drug treatment)) OR (pharmacologic therapy OR pharmacologic lowering of 

blood pressure)

#4 Combine #1 AND #2 AND #3

#5 Limit to RCTs #4 AND (randomized controlled trial* [tiab] OR randomized control trial*[tiab] OR

random*[tiab] OR single blind*[tiab] OR double blind* [tiab])

#6

Apply language 

limit and limit to 

studies in the 

process of being 

indexed process 

of being indexed

#5 AND English[lang] AND inprocess[sb]

EMBASE

Set 

# Searched for Results

S1 EMB#(“Blood Pressure”) OR EMB#(“Hypertension” LNK dt) OR EMB#(“Systole”) OR 

EMB#(“Dystole”) 515423*

S2 Mesh#(“Blood Pressure” LNK de) OR Mesh# (“Hypertension” LNK dt) OR Mesh# 

(“Prehypertension”) OR Mesh# (“Systole”) OR Mesh# (“Dystole”) 98328*

S3 S1 OR S2 613713*

S4 Mesh#(“mortality”) OR Mesh#(“death”) OR EMB#(“Death”) OR Mesh#(“Cardiovascular Diseases” 

LNK pc) OR EMB#(“Cardiovascular Disease” LNK pc) 1183047*

S5

Mesh#(“Cardiovascular Diseases” LNK ep) OR EMB#(“Cardiovascular Disease” LNK ep) OR 

Mesh#(“Cardiovascular Diseases” LNK et) OR Mesh#(“Cardiovascular Diseases” LNK pp) OR 

EMB#(“Cardiovascular Disease” LNK et)

1142904*
October 2014 Page 68 of 135

Set 

# Searched for Results

S6 Mesh#(“Kidney” LNK pc) OR Mesh#(“Kidney” LNK ep) OR Mesh#(“Kidney” LNK et) OR 

Mesh#(“Kidney” LNK pp) OR EMB#(Kidney Failure) 269716*

S7

Mesh#(“Myocardial revascularization”) OR mesh#(“creatinine”) OR Mesh#(“Glomerular filtration 

rate”) OR EMB#(“Heart Muscle revascularization”) OR EMB#(“Creatinine”) OR EMB#(“glomerulus 

filtration rate”)

309623*

S8 S4 OR S5 OR S6 OR S7 2622712*

S9 EMB#(“Heart Muscle revascularization”) OR EMB#(“Creatinine”) OR EMB#(“glomerulus filtration 

rate”) 161775*

S10 S3 AND S8 AND S9 23141*

S11 S10 AND (abany(yes) AND pstype("Journal") AND at.exact("Article") AND la.exact("English") AND 

pd(>20061231)) 7090*

S12 S11 AND (dtype(“randomized controlled trial”) OR emb#(“randomized controlled trial”)) 718°

S13 S11 AND (dtype(“randomized controlled trial”) OR emb#(“randomized controlled trial”)) 718°

* Duplicates are removed from your search, but included in your result count.

° Duplicates are removed from your search and from your result count.

A. Cochrane CENTRAL

ID Search

#1 MeSH descriptor: [Blood Pressure] explode all trees and with qualifier(s): [Drug effects - DE]

#2 MeSH descriptor: [Hypertension] explode all trees and with qualifier(s): [Drug therapy - DT]

#3 MeSH descriptor: [Prehypertension] explode all trees

#4 MeSH descriptor: [Systole] explode all trees

#5 MeSH descriptor: [Diastole] explode all trees

#6 "hypertensive":ti,ab,kw (Word variations have been searched)

#7 prehypertensive:ti,ab,kw (Word variations have been searched)

#8 systolic pressure:ti,ab,kw (Word variations have been searched)

#9 diastolic pressure:ti,ab,kw (Word variations have been searched)

#10 arterial pressure:ti,ab,kw (Word variations have been searched)

#11 BP:ti,ab,kw (Word variations have been searched)

#12 systole (Word variations have been searched)

#13 diastole (Word variations have been searched)

#14 pressure (Word variations have been searched)

#15 mmHg (Word variations have been searched)

#16 mmHg (Word variations have been searched)

#17 #1 or #2 or #3 or #4 or #5 or (#6 or #7 or #8 or #9 or #10) or #11 or ((#12 or #13) and (#14 or #15 or #16)) 

#18 MeSH descriptor: [Mortality] explode all trees

#19 mortality:ti,ab,kw (Word variations have been searched)

#20 MeSH descriptor: [Death] explode all trees

#21 death:ti,ab,kw (Word variations have been searched)

#22 MeSH descriptor: [Morbidity] explode all trees

#23 morbidity:ti,ab,kw (Word variations have been searched)
October 2014 Page 69 of 135

ID Search

#24 MeSH descriptor: [Cause of Death] explode all trees

#25 MeSH descriptor: [Fatal Outcome] explode all trees

#26 MeSH descriptor: [Cardiovascular Diseases] explode all trees and with qualifier(s): [Prevention & control -

PC]

#27 MeSH descriptor: [Cardiovascular Diseases] explode all trees and with qualifier(s): [Epidemiology - EP]

#28 MeSH descriptor: [Cardiovascular Diseases] explode all trees and with qualifier(s): [Etiology - ET]

#29 MeSH descriptor: [Cardiovascular Diseases] explode all trees and with qualifier(s): [Physiopathology - PP]

#30 MeSH descriptor: [Coronary Disease] explode all trees and with qualifier(s): [Prevention & control - PC]

#31 MeSH descriptor: [Coronary Disease] explode all trees and with qualifier(s): [Epidemiology - EP]

#32 MeSH descriptor: [Coronary Disease] explode all trees and with qualifier(s): [Etiology - ET]

#33 MeSH descriptor: [Coronary Disease] explode all trees and with qualifier(s): [Physiopathology - PP]

#34 MeSH descriptor: [Coronary Artery Disease] explode all trees and with qualifier(s): [Prevention & control -

PC]

#35 MeSH descriptor: [Coronary Disease] explode all trees and with qualifier(s): [Epidemiology - EP]

#36 MeSH descriptor: [Coronary Disease] explode all trees and with qualifier(s): [Etiology - ET]

#37 MeSH descriptor: [Coronary Disease] explode all trees and with qualifier(s): [Physiopathology - PP]

#38 MeSH descriptor: [Myocardial Infarction] explode all trees and with qualifier(s): [Prevention & control - PC]

#39 MeSH descriptor: [Myocardial Infarction] explode all trees and with qualifier(s): [Epidemiology - EP]

#40 MeSH descriptor: [Myocardial Infarction] explode all trees and with qualifier(s): [Etiology - ET]

#41 MeSH descriptor: [Myocardial Infarction] explode all trees and with qualifier(s): [Physiopathology - PP]

#42 MeSH descriptor: [Heart Failure] explode all trees and with qualifier(s): [Prevention & control - PC]

#43 MeSH descriptor: [Heart Failure] explode all trees and with qualifier(s): [Epidemiology - EP]

#44 MeSH descriptor: [Heart Failure] explode all trees and with qualifier(s): [Etiology - ET]

#45 MeSH descriptor: [Heart Failure] explode all trees and with qualifier(s): [Physiopathology - PP]

#46 MeSH descriptor: [Cerebrovascular Disorders] explode all trees and with qualifier(s): [Prevention & control -

PC]

#47 MeSH descriptor: [Cerebrovascular Disorders] explode all trees and with qualifier(s): [Epidemiology - EP]

#48 MeSH descriptor: [Cerebrovascular Disorders] explode all trees and with qualifier(s): [Etiology - ET]

#49 MeSH descriptor: [Cerebrovascular Disorders] explode all trees and with qualifier(s): [Physiopathology - PP]

#50 MeSH descriptor: [Stroke] explode all trees and with qualifier(s): [Prevention & control - PC]

#51 MeSH descriptor: [Stroke] explode all trees and with qualifier(s): [Epidemiology - EP]

#52 MeSH descriptor: [Stroke] explode all trees and with qualifier(s): [Etiology - ET]

#53 MeSH descriptor: [Stroke] explode all trees and with qualifier(s): [Physiopathology - PP]

#54 MeSH descriptor: [Kidney] explode all trees and with qualifier(s): [Physiopathology - PP]

#55 "myocardial infarction":ti,ab,kw (Word variations have been searched)

#56 "heart failure":ti,ab,kw (Word variations have been searched)

#57 "stroke":ti,ab,kw (Word variations have been searched)

#58 cerebrovascular disorder:ti,ab,kw (Word variations have been searched)

#59 cerebrovascular event:ti,ab,kw (Word variations have been searched)

#60 "kidney failure":ti,ab,kw (Word variations have been searched)

#61 chronic kidney disease:ti,ab,kw (Word variations have been searched)

#62 CKD:ti,ab,kw (Word variations have been searched)

#63 MeSH descriptor: [Myocardial Revascularization] explode all trees
October 2014 Page 70 of 135

ID Search

#64 "myocardial revascularization":ti,ab,kw (Word variations have been searched)

#65 MeSH descriptor: [Creatinine] explode all trees

#66 creatinine:ti,ab,kw (Word variations have been searched)

#67 MeSH descriptor: [Glomerular Filtration Rate] explode all trees

#68 "Glomerular Filtration Rate":ti,ab,kw (Word variations have been searched)

#69 "GFR":ti,ab,kw (Word variations have been searched)

#70 "eGFR":ti,ab,kw (Word variations have been searched)

#71 "estGFR":ti,ab,kw (Word variations have been searched)

#72 "hospitalization":ti,ab,kw (Word variations have been searched)

#73 "Coronary Revascularization":ti,ab,kw (Word variations have been searched)

#74 "angioplasty":ti,ab,kw (Word variations have been searched)

#75 stent:ti,ab,kw (Word variations have been searched)

#76 "peripheral revascularization":ti,ab,kw (Word variations have been searched)

#77 "carotid":ti,ab,kw (Word variations have been searched)

#78 "extremity revascularization":ti,ab,kw (Word variations have been searched)

#79 "end stage renal disease":ti,ab,kw (Word variations have been searched)

#80 "ESRD":ti,ab,kw (Word variations have been searched)

#81 "aggressive therapy":ti,ab,kw (Word variations have been searched)

#82 goal:ti,ab,kw (Word variations have been searched)

#83 target:ti,ab,kw (Word variations have been searched)

#84 "mmHg":ti,ab,kw (Word variations have been searched)

#85 "mmHg":ti,ab,kw (Word variations have been searched)

#86 "morbidity":ti,ab,kw (Word variations have been searched)

#87

(#18 or #19 or #20 or #21 or #22 or #23 or #24 or #25) or (#26 or #27 or #28 or #29 or #30 or #31 or #32 or 

#33 or #34 or #35 or #36 or #37 or #38 or #39 or #40 or #41 or #42 or #43 or #44 or #45 or #46 or #47 or #48 

or #49 or #50 or #51 or #52 or #53 or #54) or (#55 or #56 or #57 or #58 or #59 or #60 or #61 or #62) or (#63 

or #64) or (#65 or #66) or (#67 or #68 or #69 or #70 or #71) or (#72 or #73 or #74 or #75 or #76 or #77 or 

#78 or #79 or #80) or ((#81 and (#82 or #83) and (#84 or #85)) or #86) 

#88 MeSH descriptor: [Antihypertensive Agents] explode all trees and with qualifier(s): [Therapeutic use - TU]

#89 MeSH descriptor: [Hypertension] explode all trees and with qualifier(s): [Drug therapy - DT]

#90 "antihypertensive" (Word variations have been searched)

#91 anti-hypertensive:ti,ab,kw (Word variations have been searched)

Key Questions 3 and 4

Date parameters ranged from 1966 to present. This was the date range used by the Eighth Joint National 

Committee (JNC 8) for the 2014 Evidence-based guideline for the management of high blood pressure in 

adults.11 Since KQ 3-4 was identical to one of the questions addressed in the JNC 8 guideline, we utilized 

the evidence base from the JNC 8 evidence report which covered the years 1966-2010 and then 

conducted our own search from 2010 to present.

11 James P, Oparil S, Carter B, Cushman W, 2014 evidence-based guideline for the management of high blood 

pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). 

JAMA 2013; 311(5):507-20.
October 2014 Page 71 of 135

PubMed 

1. Indexed Studies

Concept(s) Search Statement

#1 Outcomes of 

interest

(Mortality[mh] OR mortality[tiab] OR Death[mh] OR death*[tiab] OR Morbidity[mh] OR 

morbidity[tiab] OR Cause of Death[mh] OR Fatal Outcome[mh])

#2

(Cardiovascular Diseases/prevention[mh] OR Cardiovascular Diseases/epidemiology[mh] 

OR Cardiovascular Diseases/etiology[mh] OR Cardiovascular 

Diseases/physiopathology[mh] OR Coronary Disease/prevention[mh] OR Coronary 

Disease/epidemiology[mh] Coronary Disease/etiology[mh] OR Coronary 

Disease/physiopathology[mh] OR Coronary Artery Disease/prevention[mh] OR Coronary 

Artery Disease/epidemiology[mh] OR Coronary Artery Disease/etiology[mh] OR 

Coronary Artery Disease/physiopathology[mh] OR Myocardial Infarction/prevention[mh] 

OR Myocardial Infarction/epidemiology[mh] OR Myocardial Infarction/etiology[mh] OR 

Myocardial Infarction/physiopathology[mh] OR Heart Failure/prevention[mh] OR Heart 

Failure/epidemiology[mh] OR Heart Failure/etiology[mh] OR Heart 

Failure/physiopathology[mh] OR Cerebrovascular Disorders/prevention[mh] OR 

Cerebrovascular Disorders/epidemiology[mh] OR Cerebrovascular 

Disorders/etiology[mh] OR Cerebrovascular Disorders/physiopathology[mh] OR 

Stroke/prevention[mh] OR Stroke/epidemiology[mh] OR Stroke/etiology[mh] OR 

Stroke/physiopathology[mh] OR Kidney/epidemiology[mh] OR Kidney/etiology[mh] OR 

Kidney/physiopathology[mh])

#3

(myocardial infarction[tiab] OR heart failure[tiab] OR stroke[tiab] OR cerebrovascular 

disorder*[tiab] OR cerebrovascular event*[tiab] OR kidney failure[tiab] OR chronic 

kidney disease*[tiab] OR CKD[tiab])

#4 (Myocardial Revascularization [mh] OR Myocardial Revascularization[tiab])

#5 (Creatinine[mh] OR Creatinine[tiab])

#6 (Glomerular Filtration Rate[mh] OR Glomerular Filtration Rate[tiab] OR GFR[tiab] OR 

eGFR[tiab] OR estGFR[tiab])

#7

(hospitalization[tiab] OR coronary revascularization[tiab] OR angioplasty[tiab] OR 

stent*[tiab] OR peripheral revascularization[tiab] OR carotid[tiab] OR extremity 

revascularization[tiab] OR end stage renal disease[tiab] OR ESRD[tiab])

#8 (aggressive therapy[tiab] AND (goal*[tiab] OR target*[tiab]) AND (mmHg[tiab] OR 

mmHg[tiab])) OR morbidity[tiab]

#9 Antihypertensive 

treatment

((Antihypertensive Agents/therapeutic use [mh] OR Antihypertensive 

Agents/administration and dosage [mh]) OR (Hypertension/drug therapy [mh])

OR ((antihypertensive[tiab] OR anti-hypertensive[tiab]) AND drug therapy[tiab] OR drug 

treatment[tiab] OR dose[tiab] OR dosage[tiab]))

#10 Combine #1 AND (#2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8) AND #9

#11 Exclusion ((angioplasty[mh] OR angioplasty[tiab]) AND (renal artery obstruction [tiab] OR renal 

artery obstruction [mh] OR renal artery stenosis [tiab] OR renal artery stenosis[mh]))

#12 Exclusion Ocular Hypertension[mh]

#13 Combine #10 NOT (#11 OR #12)

#14 Limit to RCTs #13 AND Randomized Controlled Trial[PT]

#15 Apply date and 

language limit 

#14 AND ("1966/01/01"[PDAT] : "2013/12/14"[PDAT]) AND English[lang] 

2. Non-indexed Studies

Concept(s) Search Statement

#1 Outcomes of 

interest

mortality[tiab] OR death*[tiab] OR morbidity[tiab] OR Cause of Death[tiab] OR Fatal 

Outcome[tiab]
October 2014 Page 72 of 135

#2 Cardiovascular Diseases [tiab] OR Coronary Disease [tiab] OR Coronary Artery 

Disease[tiab]

#3

myocardial infarction[tiab] OR heart failure[tiab] OR stroke[tiab] OR cerebrovascular 

disorder*[tiab] OR cerebrovascular event*[tiab] OR kidney failure[tiab] OR chronic 

kidney disease*[tiab] OR CKD[tiab]

#4 Myocardial Revascularization[tiab]

#5 Creatinine[tiab]

#6 Glomerular Filtration Rate[tiab] OR GFR[tiab] OR eGFR[tiab] OR estGFR[tiab]

#7

hospitalization[tiab] OR coronary revascularization[tiab] OR angioplasty[tiab] OR 

stent*[tiab] OR peripheral revascularization[tiab] OR carotid[tiab] OR extremity 

revascularization[tiab] OR end stage renal disease[tiab] OR ESRD[tiab]

#8 ((aggressive therapy[tiab] AND (goal*[tiab] OR target*[tiab]) AND (mmHg[tiab] OR 

mmHg[tiab])) OR morbidity[tiab])

#9 Antihypertensive 

Treatment

(antihypertensive[tiab] OR anti-hypertensive[tiab]) AND (drug therapy[tiab] OR drug 

treatment[tiab] OR dose[tiab] OR dosage[tiab])

#10 Combine #1 AND (#2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8) AND #9

#11 Exclusion (angioplasty[tiab] AND (renal artery obstruction [tiab] OR renal artery stenosis [tiab]))

#12 Exclusion Ocular Hypertension[tiab]

#13 Combine #10 NOT (#11 OR #12)

#14 Limit to RCTs #13 AND (randomized controlled trial* [tiab] OR randomized control trial*[tiab] OR 

random*[tiab] OR single blind*[tiab] OR double blind* [tiab])

#15

Apply language 

limit and limit to 

studies in the 

process of being 

indexed

#14 AND English[lang] AND inprocess[sb]

EMBASE

Set 

# Searched for Results

S1 EMB.EXACT.EXPLODE("death") AND (abany(yes) AND pstype("Journal") AND at.exact("Article") 

AND la.exact("English")) AND pd(20100101-20141231) 44719*

S2 (Mesh.exact.explode("mortality") OR mesh.exact.explode("death")) AND (abany(yes) AND 

pstype("Journal") AND at.exact("Article") AND la.exact("English")) AND pd(20100101-20141231) 52875*

S3 (S1 OR S2) AND (abany(yes) AND pstype("Journal") AND at.exact("Article") AND 

la.exact("English")) AND pd(20100101-20141231) 97594*

S4

(EMB.EXACT.EXPLODE("cardiovascular disease -- prevention") OR 

EMB.EXACT.EXPLODE("cardiovascular disease -- epidemiology") OR 

EMB.EXACT.EXPLODE("cardiovascular disease -- etiology")) AND (abany(yes) AND 

pstype("Journal") AND at.exact("Article") AND la.exact("English")) AND pd(20100101-20141231)

38813*

S5

(Mesh.exact.explode("Cardiovascular Diseases" LNK pc) OR Mesh.exact.explode("Cardiovascular 

Diseases" LNK ep) OR Mesh.exact.explode("Cardiovascular Diseases" LNK et) OR 

Mesh.exact.explode("Cardiovascular Diseases" LNK pp)) AND (abany(yes) AND pstype("Journal") 

AND at.exact("Article") AND la.exact("English")) AND pd(20100101-20141231)

97489*

S6 (S4 OR S5) AND (abany(yes) AND pstype("Journal") AND at.exact("Article") AND 

la.exact("English")) AND pd(20100101-20141231) 136302*
October 2014 Page 73 of 135

Set 

# Searched for Results

S7

((Mesh.exact.explode("Kidney" LNK ep) OR Mesh.exact.explode("Kidney" LNK et) OR 

Mesh.exact.explode("Kidney" LNK pp)) OR EMB.exact.explode("Kidney Failure")) AND 

(abany(yes) AND pstype("Journal") AND at.exact("Article") AND la.exact("English")) AND 

pd(20100101-20141231)

26203*

S8

(EMB.EXACT("heart muscle revascularization") OR emb.exact("Creatinine") OR 

emb.exact("glomerulus filtration rate")) AND (abany(yes) AND pstype("Journal") AND 

at.exact("Article") AND la.exact("English")) AND pd(20100101-20141231)

29129*

S9 Mesh#(”Myocardial revascularization”) OR Mesh#(“creatinine”) OR Mesh#(“glomerular Filtration 

Rate”) ? 147873*

S10 S8 OR S9 177002*

S11 emb.exact("antihypertensive agent" LNK dt) OR (Mesh#(“antihypertensive agents” LNK tu) OR 

Mesh#(“antihypertensive agents” LNK dt)) OR (Mesh#("Hypertension" LNK dt)) 135520*

S12 (S2 OR S6 OR S7 OR S9) AND S11 8013*

S13 emb.exact("angioplasty") OR emb.exact("kidney artery stenosis") OR emb.exact("intraocular 

hypertension") 39083*

S14 (Mesh#("Angioplasty") OR Mesh#("Renal Artery Obstruction")) OR (Mesh#("Renal Artery 

Stenosis") OR Mesh#("Ocular Hypertension")) 104251*

S15 S13 OR S14 143334*

S16 S12 NOT S15 7610*

S17 S16 AND (dtype("randomized controlled trial") OR emb#("randomized controlled trial")) 1396°

S18 S17 AND (abany(yes) AND pstype("Journal") AND at.exact("Article") AND la.exact("English") AND 

pd(>20091231)) 724°

S19 (S3 OR S6 OR S7 OR S9) AND S11 8083*

S20 S19 NOT S15 7680*

S21 S20 AND (dtype("randomized controlled trial") OR emb#("randomized controlled trial")) 1399°

S22 S21 AND (abany(yes) AND pstype("Journal") AND at.exact("Article") AND la.exact("English") AND 

pd(>20091231)) 727°

S23 S22 NOT S16 4°

* Duplicates are removed from your search, but included in your result count.

° Duplicates are removed from your search and from your result count.

Cochrane CENTRAL

ID Search

#1 MeSH descriptor: [Mortality] explode all trees

#2 "mortality":ti,ab,kw (Word variations have been searched)

#3 MeSH descriptor: [Death] explode all trees

#4 death:ti,ab,kw (Word variations have been searched)

#5 MeSH descriptor: [Morbidity] explode all trees

#6 "morbidity":ti,ab,kw (Word variations have been searched)

#7 MeSH descriptor: [Cause of Death] explode all trees
October 2014 Page 74 of 135

ID Search

#8 MeSH descriptor: [Fatal Outcome] explode all trees

#9 (#1 or #2 or #3 or #4 or #5 or #6 or #7 or #8) 

#10 MeSH descriptor: [Cardiovascular Diseases] explode all trees and with qualifier(s): [Prevention & control -

PC]

#11 MeSH descriptor: [Cardiovascular Diseases] explode all trees and with qualifier(s): [Epidemiology - EP]

#12 MeSH descriptor: [Cardiovascular Diseases] explode all trees and with qualifier(s): [Etiology - ET]

#13 MeSH descriptor: [Cardiovascular Diseases] explode all trees and with qualifier(s): [Physiopathology - PP]

#14 MeSH descriptor: [Coronary Disease] explode all trees and with qualifier(s): [Prevention & control - PC]

#15 MeSH descriptor: [Coronary Disease] explode all trees and with qualifier(s): [Epidemiology - EP]

#16 MeSH descriptor: [Coronary Disease] explode all trees and with qualifier(s): [Etiology - ET]

#17 MeSH descriptor: [Coronary Disease] explode all trees and with qualifier(s): [Physiopathology - PP]

#18 MeSH descriptor: [Coronary Artery Disease] explode all trees and with qualifier(s): [Prevention & control -

PC]

#19 MeSH descriptor: [Coronary Artery Disease] explode all trees and with qualifier(s): [Epidemiology - EP]

#20 MeSH descriptor: [Coronary Artery Disease] explode all trees and with qualifier(s): [Etiology - ET]

#21 MeSH descriptor: [Coronary Artery Disease] explode all trees and with qualifier(s): [Physiopathology - PP]

#22 MeSH descriptor: [Myocardial Infarction] explode all trees and with qualifier(s): [Prevention & control - PC]

#23 MeSH descriptor: [Myocardial Infarction] explode all trees and with qualifier(s): [Epidemiology - EP]

#24 MeSH descriptor: [Myocardial Infarction] explode all trees and with qualifier(s): [Etiology - ET]

#25 MeSH descriptor: [Myocardial Infarction] explode all trees and with qualifier(s): [Physiopathology - PP]

#26 MeSH descriptor: [Heart Failure] explode all trees and with qualifier(s): [Prevention & control - PC]

#27 MeSH descriptor: [Heart Failure] explode all trees and with qualifier(s): [Epidemiology - EP]

#28 MeSH descriptor: [Heart Failure] explode all trees and with qualifier(s): [Etiology - ET]

#29 MeSH descriptor: [Heart Failure] explode all trees and with qualifier(s): [Physiopathology - PP]

#30 MeSH descriptor: [Cerebrovascular Disorders] explode all trees and with qualifier(s): [Prevention & control -

PC]

#31 MeSH descriptor: [Cerebrovascular Disorders] explode all trees and with qualifier(s): [Epidemiology - EP]

#32 MeSH descriptor: [Cerebrovascular Disorders] explode all trees and with qualifier(s): [Etiology - ET]

#33 MeSH descriptor: [Cerebrovascular Disorders] explode all trees and with qualifier(s): [Physiopathology - PP]

#34 MeSH descriptor: [Stroke] explode all trees and with qualifier(s): [Prevention & control - PC]

#35 MeSH descriptor: [Stroke] explode all trees and with qualifier(s): [Epidemiology - EP]

#36 MeSH descriptor: [Stroke] explode all trees and with qualifier(s): [Etiology - ET]

#37 MeSH descriptor: [Stroke] explode all trees and with qualifier(s): [Physiopathology - PP]

#38 MeSH descriptor: [Kidney] explode all trees

#39 MeSH descriptor: [Kidney] explode all trees and with qualifier(s): [Physiopathology - PP]

#40 (#10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or 

#25 or #26 or #27 or #28 or #29 or #30 or #31 or #32 or #33 or #34 or #35 or #36 or #37 or #38 or #39) 

#41 "myocardial infarction":ti,ab,kw (Word variations have been searched)

#42 heart failure:ti,ab,kw (Word variations have been searched)

#43 stroke:ti,ab,kw (Word variations have been searched)

#44 cerebrovascular disorder:ti,ab,kw (Word variations have been searched)

#45 cerebrovascular event:ti,ab,kw (Word variations have been searched)

#46 "kidney failure":ti,ab,kw (Word variations have been searched)
October 2014 Page 75 of 135

ID Search

#47 chronic kidney disease:ti,ab,kw (Word variations have been searched)

#48 CKD:ti,ab,kw (Word variations have been searched)

#49 (#41 or #42 or #43 or #44 or #45 or #46 or #47 or #48) 

#50 MeSH descriptor: [Myocardial Infarction] explode all trees

#51 "myocardial revascularization":ti,ab,kw (Word variations have been searched)

#52 (#50 or #51) 

#53 MeSH descriptor: [Creatinine] explode all trees

#54 creatinine:ti,ab,kw (Word variations have been searched)

#55 (#53 or #54) 

#56 MeSH descriptor: [Glomerular Filtration Rate] explode all trees

#57 "glomerular filtration rate":ti,ab,kw (Word variations have been searched)

#58 GFR:ti,ab,kw (Word variations have been searched)

#59 eGFR:ti,ab,kw (Word variations have been searched)

#60 estGFR:ti,ab,kw (Word variations have been searched)

#61 (#56 or #57 or #58 or #59 or #60) 

#62 "hospitalization":ti,ab,kw (Word variations have been searched)

#63 "coronary revascularization":ti,ab,kw (Word variations have been searched)

#64 angioplasty:ti,ab,kw (Word variations have been searched)

#65 "stent":ti,ab,kw (Word variations have been searched)

#66 "peripheral revascularization":ti,ab,kw (Word variations have been searched)

#67 "carotid":ti,ab,kw (Word variations have been searched)

#68 "extremity revascularization":ti,ab,kw (Word variations have been searched)

#69 "end stage renal disease":ti,ab,kw (Word variations have been searched)

#70 ESRD:ti,ab,kw (Word variations have been searched)

#71 (#62 or #63 or #64 or #65 or #66 or #67 or #68 or #69 or #70) 

#72 aggressive therapy:ti,ab,kw (Word variations have been searched)

#73 goal:ti,ab,kw (Word variations have been searched)

#74 target:ti,ab,kw (Word variations have been searched)

#75 mmHg:ti,ab,kw (Word variations have been searched)

#76 mmHg:ti,ab,kw (Word variations have been searched)

#77 "morbidity":ti,ab,kw (Word variations have been searched)

#78 (#72 and (#73 or #74) and (#75 or #76)) or #77 

#79 MeSH descriptor: [Antihypertensive Agents] explode all trees and with qualifier(s): [Therapeutic use - TU]

#80 MeSH descriptor: [Antihypertensive Agents] explode all trees and with qualifier(s): [Administration & 

dosage - AD]

#81 MeSH descriptor: [Hypertension] explode all trees and with qualifier(s): [Drug therapy - DT]

#82 "antihypertensive":ti,ab,kw (Word variations have been searched)

#83 "anti-hypertensive":ti,ab,kw (Word variations have been searched)

#84 "drug therapy":ti,ab,kw (Word variations have been searched)

#85 "drug treatment":ti,ab,kw (Word variations have been searched)

#86 dose:ti,ab,kw (Word variations have been searched)

#87 "dosage":ti,ab,kw (Word variations have been searched)
October 2014 Page 76 of 135

ID Search

#88 ((#79 or #80) or (#81) or ((#82 or #83) and #84 or #85 or #86 or #87)) 

#89 MeSH descriptor: [Angioplasty] explode all trees

#90 "angioplasty":ti,ab,kw (Word variations have been searched)

#91 "renal artery obstruction":ti,ab,kw (Word variations have been searched)

#92 MeSH descriptor: [Renal Artery Obstruction] explode all trees

#93 "renal artery stenosis":ti,ab,kw (Word variations have been searched)

#94 MeSH descriptor: [Ocular Hypertension] explode all trees

#95 ((#89 or #90) and (#91 or #92 or #93)) 

#96 ((#9 or #40 or #49 or #52 or #55 or #61 or #71 or #78) and #88) not (#95 or #94) 

#97 #96 not pubmed:an 

#98 "randomized controlled trial":pt (Word variations have been searched)

#99 #97 and #98 from 2010 to 2013

#10

0 #99 not pubmed:an

Key Question 5

It was determined that date parameters would range from 1983 to present as seminal literature on this 

topic began to be published in the mid-1980s. 

PubMed 

1. Indexed Studies

Concept(s) Search Statement

#1 Blood pressure 

monitoring Blood Pressure Determination[mh] OR Blood Pressure Monitoring, Ambulatory[mh]

#2 Test 

characteristics

Predictive Value of Tests[mh] OR Prognosis[mh] OR Sensitivity[mh] OR Specificity[mh] OR 

Hypertension/diagnosis[mh] OR prognos*[tiab] OR predictive value[tiab]

#3 Combine #1 AND #2

#4

Limit to clinical 

trial and 

observational 

study types

#3 AND Clinical Trial[PT] OR Epidemiologic Studies[mh] OR Comparative Study[PT]

#5

Apply date and 

language limit 

to clinical trials 

and 

observational 

studies

#4 AND ("1983/01/01"[PDAT] : "2014/01/09"[PDAT]) AND English[lang]

2. Non-indexed Studies

Concept(s) Search Statement

#1 Blood pressure 

monitoring

Blood Pressure Determination[tiab] OR Blood Pressure Monitoring[tiab] OR ((ambulatory 

OR office [tiab] OR home[tiab]) AND (blood pressure[tiab]))

#2 Test 

characterisics

Predictive Value[tiab] OR Prognos*[tiab] OR Sensitivity[tiab] OR Specificity[tiab] OR 

(Hypertension[tiab] AND diagnosis[tiab])
October 2014 Page 77 of 135

#3

Apply language 

limit and limit 

to studies in 

the process of 

being indexed

English[lang] AND inprocess[sb]

EMBASE

Set 

# Searched for Results 

S1 MJEMB.EXACT("blood pressure monitoring") OR EMB.EXACT("blood pressure measurement") 40191*

S2 mesh#("Blood Pressure Determination") OR mesh#("Blood Pressure Monitoring, Ambulatory") 23421*

S3 S1 OR S2 63612*

S4 EMB.EXACT("predictive value") OR EMB.EXACT("prognosis") OR EMB.EXACT("sensitivity and 

specificity") 692031*

S5 mesh#("Predictive Value of Tests") OR mesh#("Prognosis") OR mesh#("Sensitivity") OR 

mesh#("Specificity") 1142189*

S6 S4 OR S5 1834220*

S7

emb#("Clinical Study") OR (EMB.EXACT.EXPLODE("comparative study") OR EMB.EXACT("meta 

analysis") OR EMB.EXACT("systematic review")) OR (EMB.EXACT.EXPLODE("controlled study") 

OR EMB.EXACT("cohort analysis") OR EMB.EXACT("cross-sectional study"))

10151018*

S8 (dtype("Clinical Trial") OR dtype("Meta-Analysis") OR Mesh#("Epidemiologic Studies") OR 

dtype("Comparative Study")) 3253809*

S9 dtype("Review") AND ti,ab(method* OR systematic OR comprehensive) 592496*

S10 S3 AND S6 5085*

S11 S10 AND (S7 OR S8 OR S9) 3063°

S12 EMB.EXACT.EXPLODE("clinical trial") OR EMB.EXACT("longitudinal study") OR 

EMB.EXACT("retrospective study") OR EMB.EXACT("case control study") 1505398*

S13

(EMB.EXACT.EXPLODE("comparative study") OR EMB.EXACT("meta analysis") OR 

EMB.EXACT("systematic review") OR EMB.EXACT("cohort analysis") OR EMB.EXACT("crosssectional study"))1468404*

S14 S10 AND (S12 OR S13 OR S9 OR S8) 2534°

S15 S14 AND (abany(yes) AND pstype("Journal") AND at.exact("Article") AND la.exact("English")) 2006°

S16 (S14 AND (abany(yes) AND pstype("Journal") AND at.exact("Article") AND la.exact("English")) ) 

AND pd(19830101-20141231) 2002°

S17 S16 NOT SU("Medline") 1921°

S18 (EMB.EXACT.EXPLODE("comparative study") OR EMB.EXACT("meta analysis") OR 

EMB.EXACT("systematic review") OR EMB.EXACT("cross-sectional study")) 1322093*

S19 S10 AND (S18 OR S12 OR S8 OR S9) 2490°

S20 S19 NOT SU(Medline) 2343°

S21 S20 AND abany(yes) 2173°
October 2014 Page 78 of 135

S22 (S20 AND abany(yes)) AND rtype.exact("Journal Article") 1817°

S23 (S20 AND abany(yes)) AND (rtype.exact("Journal Article") AND la.exact("ENG")) 1673°

S24 (S20 AND abany(yes)) AND (rtype.exact("Journal Article") AND la.exact("ENG") AND 

pd(19830101-20141231)) 1669°

S25 (S14 AND (abany(yes) AND pstype("Journal") AND at.exact("Article") AND la.exact("English")) ) 

AND rtype.exact("Journal Article") 1673°

S26 (S10 AND (S12 OR S13 OR S9 OR S8)) AND at.exact("Article") 2325°

S27 (S10 AND (S12 OR S13 OR S9 OR S8)) AND (at.exact("Article") AND la.exact("ENG")) 2102°

S28 S27 NOT SU("Medline") 2012°

S29 (S27 NOT SU("Medline")) AND rtype.exact("Journal Article") 1713°

S30 S27 NOT SU("Medline") 2012°

S31 (S27 NOT SU("Medline")) AND at.exact("Article") 2012°

* Duplicates are removed from your search, but included in your result count.

° Duplicates are removed from your search and from your result count.

Cochrane CENTRAL

ID Search Hits 

#1 MeSH descriptor: [Blood Pressure Determination] explode all trees 1802

#2 MeSH descriptor: [Blood Pressure Monitoring, Ambulatory] explode all trees 1029

#3 MeSH descriptor: [Predictive Value of Tests] explode all trees 5651

#4 MeSH descriptor: [Blood Pressure Determination] explode all trees 1802

#5 MeSH descriptor: [Hypertension] explode all trees and with qualifier(s): [Diagnosis - DI] 637

#6 MeSH descriptor: [Prognosis] explode all trees 102019

#7 MeSH descriptor: [Sensitivity and Specificity] explode all trees 14938

#8 (#1 or #2) and (#3 or #4 or #5 or #6 or #7) from 1983 to 2014 1710

#9 Pubmed:an 421700

#10 #8 not #9 101

Key Question 6

Date parameters ranged from 2002 to present as the interventions addressed in KQ 6 were also 

addressed in the 2004 HTN CPG. The evidence report for the previous version of the hypertension 

guideline reviewed evidence through May 2002. 

A. Weight Reduction

1. PubMed Indexed Studies

Concept(s) Search Statement

#1 Weight 

reduction 

("Obesity/diet therapy"[Mesh] OR "Obesity/prevention and control"[Mesh] OR

"Obesity/therapy"[Mesh] ) OR ("Overweight/diet therapy"[Mesh] OR 

"Overweight/prevention and control"[Mesh] OR "Overweight/therapy"[Mesh]) OR "Weight 

Loss"[Mesh] OR "Diet, Reducing"[Mesh] OR "Weight Reduction Programs"[Mesh] OR obesity 

treatment*[tiab] OR weight loss*[tiab] OR weight management*[tiab]
October 2014 Page 79 of 135

#2 Blood 

pressure

Blood Pressure[mesh] OR "Hypertension"[Mesh] OR Prehypertension[mh] OR Systole[mh] 

OR Diastole[mh] OR hypertens*[tiab] OR prehypertens*[tiab] OR systolic pressure*[tiab] OR 

diastolic pressure*[tiab] OR arterial pressure*[tiab] OR blood pressure [tiab] OR BP[tiab] OR 

((systol* OR diastol*) AND (pressure* OR mmHg OR mmHg)) 

#3 Combine #1 AND #2

#4 Limit to RCTs #3 AND Randomized Controlled Trial[PT]

#5

Apply date 

and language 

limit to RCTs

#4 AND ("2002/05/01"[PDAT] : "2014/01/26"[PDAT]) AND English[lang]

2. PubMed Non-indexed Studies

Concept(s) Search Statement

#1 Weight 

reduction

Obesity[tiab] OR Overweight[tiab] OR Weight Reduc*[tiab] OR obesity treatment*[tiab] OR 

overweight treatment*[tiab] OR weight loss*[tiab] OR weight management*[tiab]

#2 Blood 

pressure

Blood Pressure[tiab] OR Hypertension[tiab] OR Prehypertension[tiab] OR Systole[tiab] OR 

Diastole[tiab] OR hypertens*[tiab] OR prehypertens*[tiab] OR systolic pressure*[tiab] OR 

diastolic pressure*[tiab] OR arterial pressure*[tiab] OR blood pressure [tiab] OR BP[tiab] OR 

((systol* OR diastol*) AND (pressure* OR mmHg OR mmHg)) 

#3 Combine #1 AND #2

#4 Limit to RCTs #3 AND (randomized controlled trial* [tiab] OR randomized control trial*[tiab] OR 

random*[tiab] OR single blind*[tiab] OR double blind* [tiab])

#5

Apply 

language 

limit and limit 

to studies in 

the process 

of being 

indexed

#4 AND English[lang] AND inprocess[sb]

3. EMBASE

Set 

# Searched For Results

S1 mesh#("Blood Pressure") OR mesh#("Hypertension") OR mesh#("Prehypertension") OR 

Mesh#("Systole") OR Mesh#("Diastole") 426964*

S2 emb#("Blood Pressure") OR emb#("Hypertension") OR emb#("Systole") OR emb#("Diastole") 844407*

S3 S1 OR S2 1271371*

S4 dtype("Randomized Controlled Trial") OR emb#("Randomized Controlled Trial") 725446*

S5

(Mesh#("Obesity" LNK DT)) OR (Mesh#("Obesity" LNK PC)) OR (Mesh#("Obesity" LNK TH)) OR 

(Mesh#("Overweight" LNK DT)) OR (Mesh#("Overweight" LNK PC)) OR (Mesh#("Overweight" LNK 

TH))

29899*

S6 Mesh#("Weight Loss") OR Mesh#("Diet, Reducing") OR Mesh#("Weight Loss Reduction 

Programs") 33383*

S7 EMB.EXACT.EXPLODE("obesity -- therapy") OR EMB.EXACT("obesity -- prevention") 25891*

S8 EMB.EXACT("obesity") AND EMB.EXACT.EXPLODE("diet therapy") 29936*

S9 EMB.EXACT.EXPLODE("weight reduction") OR EMB.EXACT.EXPLODE("diet restriction") 188196*

S10 S5 OR S6 OR S7 OR S8 OR S9 268686*
October 2014 Page 80 of 135

Set 

# Searched For Results

S11 S3 AND S4 AND S10 2393°

S12 (S3 AND S4 AND S10) AND rtype.exact("Journal Article") 625°

S13 (S3 AND S4 AND S10) AND (rtype.exact("Journal Article") AND la.exact("ENG")) 612°

S14 (S3 AND S4 AND S10) AND (rtype.exact("Journal Article") AND la.exact("ENG") AND 

pd(20020501-20140207)) 399°

* Duplicates are removed from your search, but included in your result count.

° Duplicates are removed from your search and from your result count.

4. Cochrane CENTRAL

ID Search Hits 

#1 MeSH descriptor: [Blood Pressure] explode all trees 22608

#2 MeSH descriptor: [Hypertension] explode all trees 13629

#3 MeSH descriptor: [Prehypertension] explode all trees 29

#4 MeSH descriptor: [Systole] explode all trees 1153

#5 MeSH descriptor: [Diastole] explode all trees 909

#6 hypertens*:ti,ab or prehypertens*:ti,ab or "systolic pressure" *:ti,ab or "diastolic pressure" 

*:ti,ab or "arterial pressure" *:ti,ab or "blood pressure":ti,ab or BP;ti,ab 51569

#7 ((systol*:ti,ab or diastol*:ti,ab) and (pressure*;ti,ab or mm*Hg;ti,ab)) 7 

#8 #1 or #2 or #3 or #4 or #5 or #6 or #7 58762

#9

[mh obesity/DH] or [mh obesity/PC] or [mh obesity/TH] or [mh overweight/DH] or [mh 

overweight/PC] or [mh overweight/TH] or [mh "weight loss"] or [mh "diet, reducing"] or [mh 

"weight reduction programs"] or "obesity treatment" *:ti,ab or "weight loss" *:ti,ab or "weight 

management" *:ti,ab 

9115

#10 #8 and #9 and randomized controlled trial:pt from 2002 to 2014, in Trials 676

#11 #10 not Pubmed:an 308

B. Alcohol Intake

1. PubMed Indexed Studies

Concept(s) Search Statement

#1 Alcohol 

intake

("Alcoholism/diet therapy"[Mesh] OR "Alcoholism/education"[Mesh] OR 

"Alcoholism/prevention and control"[Mesh] OR "Alcoholism/therapy"[Mesh] ) OR 

"Ethanol"[Mesh] OR "Alcoholic Beverages"[Mesh] OR "Drinking Behavior"[Mesh] OR 

ethanol*[tiab] OR alcohol*[tiab]

#2 Blood 

pressure

Blood Pressure[mesh] OR "Hypertension"[Mesh] OR Prehypertension[mh] OR Systole[mh] 

OR Diastole[mh] OR hypertens*[tiab] OR prehypertens*[tiab] OR systolic pressure*[tiab] OR 

diastolic pressure*[tiab] OR arterial pressure*[tiab] OR blood pressure [tiab] OR BP[tiab] OR 

((systol* OR diastol*) AND (pressure* OR mmHg OR mmHg)) 

#3 Combine #1 AND #2

#4 Limit to RCTs #3 AND Randomized Controlled Trial[PT]

#5

Apply date 

and language 

limit to RCTs

#4 AND ("2002/05/01"[PDAT] : "2014/01/26"[PDAT]) AND English[lang]

2. PubMed Non-indexed Studies
October 2014 Page 81 of 135

Concept(s) Search Statement 

#1 Alcohol 

intake

Alcoholism[tiab] OR Alcoholic Beverages[tiab] OR Drinking Behavior[tiab] OR ethanol*[tiab] 

OR alcohol*[tiab]

#2 Blood 

pressure

Blood Pressure[tiab] OR Hypertension[tiab] OR Prehypertension[tiab] OR Systole[tiab] OR 

Diastole[tiab] OR hypertens*[tiab] OR prehypertens*[tiab] OR systolic pressure*[tiab] OR 

diastolic pressure*[tiab] OR arterial pressure*[tiab] OR blood pressure [tiab] OR BP[tiab] OR 

((systol* OR diastol*) AND (pressure* OR mmHg OR mmHg)) 

#3 Combine #1 AND #2

#4 Limit to RCTs #3 AND (randomized controlled trial* [tiab] OR randomized control trial*[tiab] OR 

random*[tiab] OR single blind*[tiab] OR double blind* [tiab])

#5

Apply 

language 

limit and limit 

to studies in 

the process 

of being 

indexed

#4 AND English[lang] AND inprocess[sb]

3. EMBASE

Set 

# Searched for Results

S1 mesh#("Blood Pressure") OR mesh#("Hypertension") OR mesh#("Prehypertension") OR 

Mesh#("Systole") OR Mesh#("Diastole") 426939*

S2 emb#("Blood Pressure") OR emb#("Hypertension") OR emb#("Systole") OR emb#("Diastole") 844264*

S3 S1 OR S2 1271203*

S10 dtype("Randomized Controlled Trial") OR emb#("Randomized Controlled Trial") 725294*

S12

(mesh#("alcoholism" LNK DT)) OR (mesh#("alcoholism" LNK ED)) OR (mesh#("Alcoholism" LNK 

PC)) OR (mesh#("alcoholism" LNK TH)) OR mesh#("Ethanol") OR mesh#("Alcoholic Beverages") 

OR mesh#("Drinking Behavior")

353821*

S13 EMB.EXACT("alcoholism -- prevention") OR EMB.EXACT("alcoholism -- therapy") 10786*

S14 EMB.EXACT.EXPLODE("alcoholic beverage") AND EMB.EXACT.EXPLODE("drinking behavior") 2139°

S15 (EMB.EXACT.EXPLODE("education") OR EMB#("Diet Therapy")) AND EMB#("alcoholism") 7854*

S16 S12 OR S13 OR S14 OR S15 372939*

S17 S3 AND S10 AND S16 1969°

S18 (S3 AND S10 AND S16) AND la.exact("ENG") 1871°

S19 (S3 AND S10 AND S16) AND (la.exact("ENG") AND pd(20020501-20140206)) 524°

S20 (S3 AND S10 AND S16) AND (rtype.exact("Journal Article") AND la.exact("ENG") AND 

pd(20020501-20140206)) 512°

S21 EM 266968*

S22 emb#("drinking behavior") OR emb#("alcoholic beverage") 55924*

S23 S12 OR S13 OR S22 OR S15 423914*
October 2014 Page 82 of 135

S24 S23 AND S3 AND S10 1992°

S25 (S23 AND S3 AND S10) AND rtype.exact("Journal Article") 1951°

S26 (S23 AND S3 AND S10) AND (rtype.exact("Journal Article") AND pd(20020501-20140206)) 523°

S27 (S23 AND S3 AND S10) AND (rtype.exact("Journal Article") AND la.exact("ENG") AND 

pd(20020501-20140206)) 512°

S28 (S23 AND S3 AND S10) AND (rtype.exact("Journal Article") AND la.exact("ENG") AND 

subt.exact("humans") AND pd(20020501-20140206)) 506°

* Duplicates are removed from your search, but included in your result count.

° Duplicates are removed from your search and from your result count.

4. Cochrane CENTRAL

ID Search Hits 

#1

[mh "blood pressure"] or [mh hypertension] or [mh prehypertension] or [mh systole] or [mh 

diastole] or (hypertens*:ti,ab or prehypertens*:ti,ab or "systolic pressure" *:ti,ab or "diastolic 

pressure" *:ti,ab or "arterial pressure" *:ti,ab or "blood pressure":ti,ab or BP;ti,ab) or 

((systol*:ti,ab or diastol*:ti,ab) and (pressure*;ti,ab or mm*Hg;ti,ab)) 

58762

#2

[mh alcoholism/DH] or [mh alcoholism/ED] or [mh alcoholism/PC] or [mh alcoholism/TH] or [mh 

ethanol] or [mh "alcoholic beverages"] or [mh "drinking behavior"] or ethanol*:ti,ab or 

alcohol*:ti,ab 

14022

#3 #1 and #2 and randomized controlled trial:pt from 2002 to 2014, in Trials 290

#4 #3 not Pubmed:an 86

C. Sodium Reduction

1. PubMed Indexed Studies

Concept(s) Search Statement

#1 Sodium 

intake

"Diet, Sodium-Restricted"[Mesh] OR "Sodium, Dietary"[Mesh] OR "Sodium Chloride, 

Dietary"[Mesh] OR sodium*[tiab] OR salt*[tiab]

#2 Blood 

pressure

Blood Pressure[mesh] OR "Hypertension"[Mesh] OR Prehypertension[mh] OR Systole[mh] 

OR Diastole[mh] OR hypertens*[tiab] OR prehypertens*[tiab] OR systolic pressure*[tiab] 

OR diastolic pressure*[tiab] OR arterial pressure*[tiab] OR blood pressure [tiab] OR 

BP[tiab] OR ((systol* OR diastol*) AND (pressure* OR mmHg OR mmHg)) 

#3 Combine #1 AND #2

#4 Limit to RCTs #3 AND Randomized Controlled Trial[PT]

#5

Apply date 

and language 

limit to RCTs

#4 AND ("2002/05/01"[PDAT] : "2014/01/26"[PDAT]) AND English[lang]

2. PubMed Non-indexed Studies

Concept(s) Search Statement

#1 Sodium 

intake

Sodium intake[tiab] OR dietary sodium[tiab] OR (dietary[tiab] AND sodium[tiab]) OR 

sodium*[tiab] OR salt*[tiab]

#2 Blood 

pressure

Blood Pressure[tiab] OR Hypertension[tiab] OR Prehypertension[tiab] OR Systole[tiab] OR 

Diastole[tiab] OR hypertens*[tiab] OR prehypertens*[tiab] OR systolic pressure*[tiab] OR 

diastolic pressure*[tiab] OR arterial pressure*[tiab] OR blood pressure [tiab] OR BP[tiab] 

OR ((systol* OR diastol*) AND (pressure* OR mmHg OR mmHg)) 

#3 Combine #1 AND #2
October 2014 Page 83 of 135

#4 Limit to RCTs #3 AND (randomized controlled trial* [tiab] OR randomized control trial*[tiab] OR 

random*[tiab] OR single blind*[tiab] OR double blind* [tiab])

#5

Apply 

language limit 

and limit to 

studies in the 

process of 

being indexed

#4 AND English[lang] AND inprocess[sb]

3. EMBASE

Set 

# Searched for Results

S1 mesh#("Blood Pressure") OR mesh#("Hypertension") OR mesh#("Prehypertension") OR 

Mesh#("Systole") OR Mesh#("Diastole") 426821*

S2 emb#("Blood Pressure") OR emb#("Hypertension") OR emb#("Systole") OR emb#("Diastole") 843597*

S3 S1 OR S2 1270421*

S7 dtype("Randomized Controlled Trial") OR emb#("Randomized Controlled Trial") 724777*

S8 mesh#("Mind-Body Therapies") OR mesh#("Mind-Body Relations, Metaphysical") OR 

mesh#("Behavior Therapy") 864123*

S9 EMB.EXACT.EXPLODE("alternative medicine") OR EMB.EXACT.EXPLODE("behavior therapy") 71569*

S10 S3 AND (S8 OR S9) 30722*

S11 S10 AND S7 2796°

S12 S11 AND (pstype("Journal") AND at.exact("Article") AND la.exact("English") AND pd(20020501-

20140204)) 1142°

S13 mesh#("Diet, Sodium-Restricted") OR mesh#("Sodiium, Dietary") OR mesh#("Sodium Chloride, 

Dietary") 8979*

S14 EMB.EXACT.EXPLODE("sodium intake") OR EMB.EXACT.EXPLODE("sodium restriction") OR 

EMB.EXACT.EXPLODE("salt intake") 20517*

S15 S13 OR S14 29496*

S16 S3 AND S15 AND S7 657°

S17 S16 AND (pstype("Journal") AND at.exact("Article") AND la.exact("English") AND pd(20020501-

20140204)) 237°

4. Cochrane CENTRAL

ID Search Hits 

#1

[mh "blood pressure"] or [mh hypertension] or [mh prehypertension] or [mh systole] or [mh 

diastole] or (hypertens*:ti,ab or prehypertens*:ti,ab or "systolic pressure" *:ti,ab or "diastolic 

pressure" *:ti,ab or "arterial pressure" *:ti,ab or "blood pressure":ti,ab or BP;ti,ab) or 

((systol*:ti,ab or diastol*:ti,ab) and (pressure*;ti,ab or mm*Hg;ti,ab)) 

58762

#2 [mh "diet, sodium-restricted"] or [mh "sodium, dietary"] or [mh "sodium chloride, dietary"] or 

sodium*:ti,ab or salt*:ti,ab 17004

#3 #1 and #2 and randomized controlled trial:pt from 2002 to 2014, in Trials 660

#4 #3 not Pubmed:an 180
October 2014 Page 84 of 135

D. Dietary and Non-Dietary Potassium

1. PubMed Indexed Studies

Concept(s) Search Statement

#1 Potassium 

intake

("Potassium/administration and dosage"[Mesh] OR "Potassium/drug effects"[Mesh] OR 

"Potassium/pharmacology"[Mesh] OR "Potassium/therapeutic use"[Mesh] OR 

"Potassium/therapy"[Mesh] ) OR "Potassium, Dietary"[Mesh] OR "Potassium 

Chloride"[Mesh] OR potassium*[tiab] 

#2 Blood 

pressure

Blood Pressure[mesh] OR "Hypertension"[Mesh] OR Prehypertension[mh] OR Systole[mh] 

OR Diastole[mh] OR hypertens*[tiab] OR prehypertens*[tiab] OR systolic pressure*[tiab] OR 

diastolic pressure*[tiab] OR arterial pressure*[tiab] OR blood pressure [tiab] OR BP[tiab] OR 

((systol* OR diastol*) AND (pressure* OR mmHg OR mmHg)) 

#3 Combine #1 AND #2

#4 Limit to RCTs #3 AND Randomized Controlled Trial[PT]

#5

Apply date 

and language 

limit to RCTs

#4 AND ("2002/05/01"[PDAT] : "2014/01/26"[PDAT]) AND English[lang]

2. PubMed Non-indexed Studies

Concept(s) Search Statement

#1 Potassium 

intake Potassium intake[tiab] OR dietary potassium[tiab] OR (dietary[tiab] AND potassium[tiab])

#2 Blood 

pressure

Blood Pressure[tiab] OR Hypertension[tiab] OR Prehypertension[tiab] OR Systole[tiab] OR 

Diastole[tiab] OR hypertens*[tiab] OR prehypertens*[tiab] OR systolic pressure*[tiab] OR 

diastolic pressure*[tiab] OR arterial pressure*[tiab] OR blood pressure [tiab] OR BP[tiab] OR 

((systol* OR diastol*) AND (pressure* OR mmHg OR mmHg)) 

#3 Combine #1 AND #2

#4 Limit to RCTs #3 AND (randomized controlled trial* [tiab] OR randomized control trial*[tiab] OR 

random*[tiab] OR single blind*[tiab] OR double blind* [tiab])

#5

Apply 

language 

limit and limit 

to studies in 

the process 

of being 

indexed

#4 AND English[lang] AND inprocess[sb]

3. EMBASE

Set 

# Searched for Results

S1 mesh#("Blood Pressure") OR mesh#("Hypertension") OR mesh#("Prehypertension") OR 

Mesh#("Systole") OR Mesh#("Diastole") 426939*

S2 emb#("Blood Pressure") OR emb#("Hypertension") OR emb#("Systole") OR emb#("Diastole") 844264*

S3 S1 OR S2 1271203*

S4

(Mesh#("Potassium" LNK AD)) OR (Mesh#("Potassium" LNK DE)) OR (Mesh#("Potassium" LNK PD) 

) OR (Mesh#("Potassium" LNK TU) ) OR (Mesh#("Potassium" LNK TH) ) OR Mesh#("Potassium, 

Dietary") OR Mesh#("Potassium Chloride")

40392*
October 2014 Page 85 of 135

S5 EMB.EXACT("potassium -- drug dose") OR EMB.EXACT("potassium -- drug administration") 1142°

S6 EMB.EXACT("potassium -- pharmacology") OR EMB.EXACT("potassium -- therapy") 7132*

S7 EMB.EXACT("potassium") AND EMB.EXACT("Drug Effect") 13731*

S8 S4 OR S5 OR S6 OR S7 57480*

S9 S3 AND S8 3342°

S10 dtype("Randomized Controlled Trial") OR emb#("Randomized Controlled Trial") 725294*

S11 S10 AND S9 313°

S12 (S10 AND S9) AND at.exact("Article") 302°

S13 (S10 AND S9) AND (at.exact("Article") AND rtype.exact("Journal Article")) 165°

S14 (S10 AND S9) AND (at.exact("Article") AND rtype.exact("Journal Article") AND pd(20020501-

20140206)) 42°

S15 EMB.EXACT.EXPLODE("potassium intake") OR EMB.EXACT("potassium chloride") 31731*

S16 S8 OR S15 88789*

S17 S16 AND S3 AND S10 367°

S18 (S16 AND S3 AND S10) AND rtype.exact("Journal Article") 165°

4. Cochrane CENTRAL

ID Search Hits 

#1

[mh "blood pressure"] or [mh hypertension] or [mh prehypertension] or [mh systole] or [mh 

diastole] or (hypertens*:ti,ab or prehypertens*:ti,ab or "systolic pressure" *:ti,ab or "diastolic 

pressure" *:ti,ab or "arterial pressure" *:ti,ab or "blood pressure":ti,ab or BP;ti,ab) or 

((systol*:ti,ab or diastol*:ti,ab) and (pressure*;ti,ab or mm*Hg;ti,ab)) 

58762

#2 [mh potassium/AD] or [mh potassium/DE] or [mh potassium/PD] or [mh potassium/TU] or [mh 

potassium/TH] or [mh "potassium, dietary"] or [mh "potassium chloride"] or potassium*:ti,ab 

5575

#3 #1 and #2 and randomized controlled trial:pt from 2002 to 2014, in Trials 344

#4 #3 NOT Pubmed:an 0

E. Combined Dietary Modification

1. PubMed Indexed Studies

Concept(s) Search Statement 

#1 Dietary 

changes

"Diet"[Mesh] OR "Food Habits"[Mesh] OR "Hypertension/diet therapy"[Mesh] OR dietary 

[tiab]

#2 Blood 

pressure

Blood Pressure[mesh] OR "Hypertension"[Mesh] OR Prehypertension[mh] OR Systole[mh] 

OR Diastole[mh] OR hypertens*[tiab] OR prehypertens*[tiab] OR systolic pressure*[tiab] OR 

diastolic pressure*[tiab] OR arterial pressure*[tiab] OR blood pressure [tiab] OR BP[tiab] OR 

((systol* OR diastol*) AND (pressure* OR mmHg OR mmHg)) 

#3 Combine #1 AND #2

#4 Limit to RCTs #3 AND Randomized Controlled Trial[PT]

#5

Apply date 

and language 

limit to RCTs

#4 AND ("2002/05/01"[PDAT] : "2014/01/26"[PDAT]) AND English[lang]
October 2014 Page 86 of 135

2. PubMed Non-indexed Studies

Concept(s) Search Statement 

#1 Dietary 

changes Diet[tiab] OR food habits[tiab] OR dietary[tiab]

#2 Blood 

pressure

Blood Pressure[tiab] OR Hypertension[tiab] OR Prehypertension[tiab] OR Systole[tiab] OR 

Diastole[tiab] OR hypertens*[tiab] OR prehypertens*[tiab] OR systolic pressure*[tiab] OR 

diastolic pressure*[tiab] OR arterial pressure*[tiab] OR blood pressure [tiab] OR BP[tiab] OR 

((systol* OR diastol*) AND (pressure* OR mmHg OR mmHg)) 

#3 Combine #1 AND #2

#4 Limit to RCTs #3 AND (randomized controlled trial* [tiab] OR randomized control trial*[tiab] OR 

random*[tiab] OR single blind*[tiab] OR double blind* [tiab])

#5

Apply 

language 

limit and limit 

to studies in 

the process 

of being 

indexed

#4 AND English[lang] AND inprocess[sb]

3. EMBASE

Set 

# Searched for Results

S1 mesh#("Blood Pressure") OR mesh#("Hypertension") OR mesh#("Prehypertension") OR 

Mesh#("Systole") OR Mesh#("Diastole") 426939*

S2 emb#("Blood Pressure") OR emb#("Hypertension") OR emb#("Systole") OR emb#("Diastole") 844264*

S3 S1 OR S2 1271203*

S10 dtype("Randomized Controlled Trial") OR emb#("Randomized Controlled Trial") 725294*

S11 mesh#("Diet") OR mesh#("Food Habits") OR (Mesh#("Hypertension" LNK DH)) 311694*

S12 (EMB.EXACT.EXPLODE("diet") OR EMB.EXACT.EXPLODE("diet therapy")) OR 

EMB.EXACT.EXPLODE("feeding behavior") 554282*

S13 S11 OR S12 865976*

S14 S3 AND S10 AND S13 3760°

S15 (S3 AND S10 AND S13) AND pd(20020501-20140206) 2510°

S16 (S3 AND S10 AND S13) AND (rtype.exact("Journal Article") AND pd(20020501-20140206)) 771°

4. Cochrane CENTRAL

ID Search Hits 

#1

[mh "blood pressure"] or [mh hypertension] or [mh prehypertension] or [mh systole] or [mh 

diastole] or (hypertens*:ti,ab or prehypertens*:ti,ab or "systolic pressure" *:ti,ab or "diastolic 

pressure" *:ti,ab or "arterial pressure" *:ti,ab or "blood pressure":ti,ab or BP;ti,ab) or 

((systol*:ti,ab or diastol*:ti,ab) and (pressure*;ti,ab or mm*Hg;ti,ab)) 

58762

#2 [mh diet] or [mh "food habits"] or [mh hypertension/DH] or dietary:ti,ab 25846

#3 #1 and #2 and randomized controlled trial:pt from 2002 to 2014, in Trials 1239

#4 #3 not Pubmed:an 215
October 2014 Page 87 of 135

F. Exercise/Physical Activity

1. PubMed Indexed Studies

Concept(s) Search Statement 

#1

Exercise/ 

physical 

activity

"Exercise"[Mesh] OR "Exercise Therapy"[Mesh] OR "Motor Activity"[Mesh] OR physical 

activ*[tiab]

#2 Blood 

pressure

Blood Pressure[mesh] OR "Hypertension"[Mesh] OR Prehypertension[mh] OR Systole[mh] 

OR Diastole[mh] OR hypertens*[tiab] OR prehypertens*[tiab] OR systolic pressure*[tiab] OR 

diastolic pressure*[tiab] OR arterial pressure*[tiab] OR blood pressure [tiab] OR BP[tiab] OR 

((systol* OR diastol*) AND (pressure* OR mmHg OR mmHg)) 

#3 Combine #1 AND #2

#4 Limit to RCTs #3 AND Randomized Controlled Trial[PT]

#5

Apply date 

and language 

limit to RCTs

#4 AND ("2002/05/01"[PDAT] : "2014/01/26"[PDAT]) AND English[lang]

2. PubMed Non-indexed Studies

Concept(s) Search Statement 

#1

Exercise/ 

physical 

activity

Exercise[tiab] OR motor activity[tiab] OR physical activ*[tiab] OR physically active[tiab] 

#2 Blood 

pressure

Blood Pressure[tiab] OR Hypertension[tiab] OR Prehypertension[tiab] OR Systole[tiab] OR 

Diastole[tiab] OR hypertens*[tiab] OR prehypertens*[tiab] OR systolic pressure*[tiab] OR 

diastolic pressure*[tiab] OR arterial pressure*[tiab] OR blood pressure [tiab] OR BP[tiab] OR 

((systol* OR diastol*) AND (pressure* OR mmHg OR mmHg)) 

#3 Combine #1 AND #2

#4 Limit to RCTs #3 AND (randomized controlled trial* [tiab] OR randomized control trial*[tiab] OR 

random*[tiab] OR single blind*[tiab] OR double blind* [tiab])

#5

Apply 

language 

limit and limit 

to studies in 

the process 

of being 

indexed

#4 AND English[lang] AND inprocess[sb]

3. EMBASE

Set # Searched for Results

S1 mesh#("Blood Pressure") OR mesh#("Hypertension") OR mesh#("Prehypertension") OR 

Mesh#("Systole") OR Mesh#("Diastole") 426821*

S2 emb#("Blood Pressure") OR emb#("Hypertension") OR emb#("Systole") OR emb#("Diastole") 843597*

S3 S1 OR S2 1270421*

S4 mesh#("Exercise") OR mesh#("Exercise Therapy") OR Mesh#("Motor Activity") 212122*

S5 EMB.EXACT.EXPLODE("exercise") OR EMB.EXACT.EXPLODE("kinesiotherapy") OR 

EMB.EXACT.EXPLODE("motor activity") 629073*

S6 S3 AND (S4 OR S5) 47352*
October 2014 Page 88 of 135

S7 dtype("Randomized Controlled Trial") OR emb#("Randomized Controlled Trial") 724777*

4. Cochrane CENTRAL

ID Search Hits 

#1

[mh "blood pressure"] or [mh hypertension] or [mh prehypertension] or [mh systole] or [mh 

diastole] or (hypertens*:ti,ab or prehypertens*:ti,ab or "systolic pressure" *:ti,ab or "diastolic 

pressure" *:ti,ab or "arterial pressure" *:ti,ab or "blood pressure":ti,ab or BP;ti,ab) or 

((systol*:ti,ab or diastol*:ti,ab) and (pressure*;ti,ab or mm*Hg;ti,ab)) 

58762

#2 [mh exercise] or [mh "exercise therapy"] or [mh "motor activity"] or "physical activ" *:ti,ab 18585

#3 #1 and #2 and randomized controlled trial:pt from 2002 to 2014, in Trials 1034

#4 #3 not Pubmed:an 228

G. Mind-Body Therapy

1. PubMed Indexed Studies

Concept(s) Search Statement 

#1 Mind- body 

interventions

"Mind-Body Therapies"[Mesh] OR "Mind-Body Relations, Metaphysical"[Mesh] OR 

"Behavior Therapy"[Mesh] OR biofeedback[tiab] OR meditat*[tiab] OR yog*[tiab] OR tai 

ji[tiab] OR t'ai chi[tiab] OR hypnosis[tiab] OR relax*[tiab] OR breath*[tiab] OR stress 

management[tiab] OR cognitive therapy[tiab] OR autogen*[tiab]

#2 Blood 

pressure

Blood Pressure[mesh] OR "Hypertension"[Mesh] OR Prehypertension[mh] OR Systole[mh] 

OR Diastole[mh] OR hypertens*[tiab] OR prehypertens*[tiab] OR systolic pressure*[tiab] OR 

diastolic pressure*[tiab] OR arterial pressure*[tiab] OR blood pressure [tiab] OR BP[tiab] OR 

((systol* OR diastol*) AND (pressure* OR mmHg OR mmHg)) 

#3 Combine #1 AND #2

#4 Limit to RCTs #3 AND Randomized Controlled Trial[PT]

#5

Apply date 

and language 

limit to RCTs

#4 AND ("2002/05/01"[PDAT] : "2014/01/26"[PDAT]) AND English[lang]

2. PubMed Non-indexed Studies

Concept(s) Search Statement 

#1 Mind- body 

interventions

Mind body[tiab] OR behavior therapy[tiab] OR biofeedback[tiab] OR meditat*[tiab] OR 

yog*[tiab] OR tai ji[tiab] OR t'ai chi[tiab] OR hypnosis[tiab] OR relax*[tiab] OR breath*[tiab] 

OR stress management[tiab] OR cognitive therapy[tiab] OR autogen*[tiab]

#2 Blood 

pressure

Blood Pressure[tiab] OR Hypertension[tiab] OR Prehypertension[tiab] OR Systole[tiab] OR 

Diastole[tiab] OR hypertens*[tiab] OR prehypertens*[tiab] OR systolic pressure*[tiab] OR 

diastolic pressure*[tiab] OR arterial pressure*[tiab] OR blood pressure [tiab] OR BP[tiab] OR 

((systol* OR diastol*) AND (pressure* OR mmHg OR mmHg)) 

#3 Combine #1 AND #2

#4 Limit to RCTs #3 AND (randomized controlled trial* [tiab] OR randomized control trial*[tiab] OR 

random*[tiab] OR single blind*[tiab] OR double blind* [tiab])

#5

Limit to 

studies in the 

process of 

being indexed 

and english

#4 AND English[lang] AND inprocess[sb]

3. EMBASE
October 2014 Page 89 of 135

Set 

# Searched for Results

S1 mesh#("Blood Pressure") OR mesh#("Hypertension") OR mesh#("Prehypertension") OR 

Mesh#("Systole") OR Mesh#("Diastole") 426821*

S2 emb#("Blood Pressure") OR emb#("Hypertension") OR emb#("Systole") OR emb#("Diastole") 843597*

S3 S1 OR S2 1270421*

S7 dtype("Randomized Controlled Trial") OR emb#("Randomized Controlled Trial") 724777*

S8 mesh#("Mind-Body Therapies") OR mesh#("Mind-Body Relations, Metaphysical") OR 

mesh#("Behavior Therapy") 864123*

S9 EMB.EXACT.EXPLODE("alternative medicine") OR EMB.EXACT.EXPLODE("behavior therapy") 71569*

S10 S3 AND (S8 OR S9) 30722*

S11 S10 AND S7 2796°

S12 S11 AND (pstype("Journal") AND at.exact("Article") AND la.exact("English") AND pd(20020501-

20140204)) 1142°

4. Cochrane CENTRAL

ID Search Hits 

#1

[mh "blood pressure"] or [mh hypertension] or [mh prehypertension] or [mh systole] or [mh 

diastole] or (hypertens*:ti,ab or prehypertens*:ti,ab or "systolic pressure" *:ti,ab or "diastolic 

pressure" *:ti,ab or "arterial pressure" *:ti,ab or "blood pressure":ti,ab or BP;ti,ab) or 

((systol*:ti,ab or diastol*:ti,ab) and (pressure*;ti,ab or mm*Hg;ti,ab)) 

58762

#2

[mh "mind-body therapies"] or [mh "mind-body relations, metaphysical"] or [mh "behavior 

therapy"] or biofeedback:ti,ab or meditat*:ti,ab or yog*:ti,ab or "tai ji":ti,ab or "t'ai chi":ti,ab or 

hypnosis:ti,ab or relax*:ti,ab or breath*:ti,ab or "stress management":ti,ab or "cognitive 

therapy":ti,ab or autogen*:ti,ab 

28279

#3 #1 and #2 and randomized controlled trial:pt from 2002 to 2014, in Trials 751

#4 #3 not Pubmed:an 105

H. Improved Adherence

1. PubMed Indexed Studies

Concept(s) Search Statement

#1 Adherence 

interventions

"Patient Compliance"[Mesh] OR "Patient Education as Topic"[Mesh] OR "Health 

Education"[Mesh] OR "Case Management"[Mesh] OR "Disease Management"[MeSH Terms] 

OR "Patient Care Management"[Mesh] OR "Patient Care Planning"[Mesh] OR "Patient 

Participation"[Mesh] OR "Reminder Systems"[Mesh] OR "Self Care"[Mesh] OR 

complian*[tiab] OR adheren*[tiab] OR self monitor*[tiab] OR self-monitor*[tiab] OR 

educat*[tiab] OR case management[tiab]

#2 Blood 

pressure

Blood Pressure[mesh] OR "Hypertension"[Mesh] OR Prehypertension[mh] OR Systole[mh] 

OR Diastole[mh] OR hypertens*[tiab] OR prehypertens*[tiab] OR systolic pressure*[tiab] OR 

diastolic pressure*[tiab] OR arterial pressure*[tiab] OR blood pressure [tiab] OR BP[tiab] OR 

((systol* OR diastol*) AND (pressure* OR mmHg OR mmHg)) 

#3 Combine #1 AND #2

#4 Limit to RCTs #3 AND Randomized Controlled Trial[PT]

#5

Apply date 

and language 

limit to RCTs

#4 AND ("2002/05/01"[PDAT] : "2014/01/26"[PDAT]) AND English[lang]
October 2014 Page 90 of 135

2. PubMed Non-indexed Studies

Concept(s) Search Statement

#1 Adherence 

interventions

patient[tiab] AND (complian*[tiab] OR adheren*[tiab] OR self monitor*[tiab] OR selfmonitor*[tiab] OR educat*[tiab] OR case management[tiab] OR management[tiab] OR 

reminder system*[tiab] OR self care[tiab] OR care planning[tiab])

#2 Blood 

pressure

Blood Pressure[tiab] OR Hypertension[tiab] OR Prehypertension[tiab] OR Systole[tiab] OR 

Diastole[tiab] OR hypertens*[tiab] OR prehypertens*[tiab] OR systolic pressure*[tiab] OR 

diastolic pressure*[tiab] OR arterial pressure*[tiab] OR blood pressure [tiab] OR BP[tiab] OR 

((systol* OR diastol*) AND (pressure* OR mmHg OR mmHg)) 

#3 Combine #1 AND #2

#4 Limit to RCTs #3 AND (randomized controlled trial* [tiab] OR randomized control trial*[tiab] OR 

random*[tiab] OR single blind*[tiab] OR double blind* [tiab])

#5

Apply 

language 

limit and limit 

to studies in 

the process 

of being 

indexed

#4 AND English[lang] AND inprocess[sb]

3. EMBASE

Set 

# Searched for Results

S1 Mesh#("Patient Compliance") OR Mesh#("Patient Education as Topic") OR Mesh#("Health 

Education") OR Mesh#("Case Management") OR Mesh#("Disease Management") 209459*

S2 Mesh#("Patient Care Management") OR Mesh#("Patient Care Planning") OR Mesh#("Patient 

Participation") OR Mesh#("Reminder Systems") OR Mesh#("Self Care") 1026946*

S3

EMB.EXACT("patient compliance") OR EMB.EXACT.EXPLODE("health education") OR 

EMB.EXACT("patient care planning") OR EMB.EXACT.EXPLODE("patient care") OR 

EMB.EXACT.EXPLODE("disease management")

2356085*

S4 EMB.EXACT.EXPLODE("reminder system") OR EMB.EXACT.EXPLODE("self care") OR 

EMB.EXACT.EXPLODE("patient satisfaction") 134928*

S5 mesh#("Blood Pressure") OR mesh#("Hypertension") OR mesh#("Prehypertension") OR 

Mesh#("Systole") OR Mesh#("Diastole") 426821*

S6 emb#("Blood Pressure") OR emb#("Hypertension") OR emb#("Systole") OR emb#("Diastole") 843569*

S7 S1 OR S2 OR S3 OR S4 3518090*

S8 S7 AND (S5 OR S6) 130997*

S9 EMB.EXACT.EXPLODE("randomized controlled trial") OR dtype("Randomized Controlled Trial") 724754*

S10 S8 AND S9 12498*

S11 (S8 AND S9) AND rtype.exact("Journal Article") 1593°

S12 pstype("Journal") AND at.exact("Article") AND la.exact("English") 35988942*

S13 (S11 AND S12) AND (pstype("Journal") AND at.exact("Article") AND la.exact("English")) 1540°

S14 (S11 AND S12) AND (pstype("Journal") AND at.exact("Article") AND la.exact("English")) 1000°
October 2014 Page 91 of 135

S15 (S11 AND S12) AND (pstype("Journal") AND at.exact("Article") AND la.exact("English") AND 

pd(20020501-20140204)) 950°

S16 (S11 AND S12) AND (pstype("Journal") AND at.exact("Article") AND la.exact("English") AND 

pd(20020501-20140204)) 950°

4. Cochrane CENTRAL

ID Search Hits 

#1

[mh "blood pressure"] or [mh hypertension] or [mh prehypertension] or [mh systole] or [mh 

diastole] or (hypertens*:ti,ab or prehypertens*:ti,ab or "systolic pressure" *:ti,ab or "diastolic 

pressure" *:ti,ab or "arterial pressure" *:ti,ab or "blood pressure":ti,ab or BP;ti,ab) or 

((systol*:ti,ab or diastol*:ti,ab) and (pressure*;ti,ab or mm*Hg;ti,ab)) 

58762

#2

[mh "patient compliance"] or [mh "patient educaton as topic"] or [mh "health education"] or 

[mh "case management"] or [mh "disease management"] or [mh "patient care management"] or 

[mh "patient care planning"] or [mh "patient participation"] or [mh "reminder systems"] or [mh 

"self care"] or complian*:ti,ab or adheren*:ti,ab or "self monitor" *:ti,ab or "self monitor" *:ti,ab 

or educat*:ti,ab or "case management":ti,ab 

55610

#3 #1 and #2 and randomized controlled trial:pt from 2002 to 2014, in Trials 1717

#4 #3 not Pubmed:an 560

Key Question 7

Date parameters ranged from 1966 to present. This was the date range used by the Eighth Joint National 

Committee (JNC 8) for the 2014 evidence-based guideline for the management of high blood pressure in 

adults.12 Since KQ 7 was indentical to one of the questions addressed in the JNC 8 guideline, we utilized 

the evidence base from the JNC 8 evidence report which covered the years 1966-2010 and then 

conducted our own search from 2010 to present. 

PubMed

1. Indexed Studies

Concept Search Statement

#1 Hypertension Hypertension[mh] OR hypertension[tiab] OR hypertensive*[tiab]

#2 Outcomes (Mortality[mh] OR mortality[tiab] OR Death[mh] OR death*[tiab] OR Morbidity[mh] OR 

morbidity[tiab] OR Cause of Death[mh] OR Fatal Outcome[mh] OR Survival Rate[mh])

12 James P, Oparil S, Carter B, Cushman W, 2014 evidence-based guideline for the management of high 

blood pressure in adults: report from the panel members appointed to the Eighth Joint National 

Committee (JNC 8). JAMA 2013; 311(5):507-20.
October 2014 Page 92 of 135

Concept Search Statement

#3

(Cardiovascular Diseases/prevention[mh] OR Cardiovascular Diseases/epidemiology[mh] OR 

Cardiovascular Diseases/etiology[mh] OR Cardiovascular Diseases/physiopathology[mh] OR 

Coronary Disease/prevention[mh] OR Coronary Disease/epidemiology[mh] Coronary 

Disease/etiology[mh] OR Coronary Disease/physiopathology[mh] OR Coronary Artery 

Disease/prevention[mh] OR Coronary Artery Disease/epidemiology[mh] OR Coronary Artery 

Disease/etiology[mh] OR Coronary Artery Disease/physiopathology[mh] OR Myocardial 

Infarction/prevention[mh] OR Myocardial Infarction/epidemiology[mh] OR Myocardial 

Infarction/etiology[mh] OR Myocardial Infarction/physiopathology[mh] OR Heart 

Failure/prevention[mh] OR Heart Failure/epidemiology[mh] OR Heart Failure/etiology[mh] 

OR Heart Failure/physiopathology[mh] OR Cerebrovascular Disorders/prevention[mh] OR 

Cerebrovascular Disorders/epidemiology[mh] OR Cerebrovascular Disorders/etiology[mh] 

OR Cerebrovascular Disorders/physiopathology[mh] OR Stroke/prevention[mh] OR 

Stroke/epidemiology[mh] OR Stroke/etiology[mh] OR Stroke/physiopathology[mh] OR

Kidney/epidemiology[mh] OR Kidney/etiology[mh] OR Kidney/physiopathology[mh])

#4

(myocardial infarction[tiab] OR heart failure[tiab] OR stroke[tiab] OR cerebrovascular 

disorder*[tiab] OR cerebrovascular event*[tiab] OR kidney failure[tiab] OR chronic kidney 

disease*[tiab] OR CKD[tiab])

#5 (Myocardial Revascularization [mh] OR Myocardial Revascularization[tiab])

#6 (Creatinine[mh] OR Creatinine[tiab])

#7 (Glomerular Filtration Rate[mh] OR Glomerular Filtration Rate[tiab] OR GFR[tiab] OR 

eGFR[tiab] OR estGFR[tiab])

#8 Treatment 

((Antihypertensive Agents/therapeutic use[mh] OR Antihypertensive Agents/adverse 

effects[mh]) OR (Hypertension/drug therapy[mh] OR Hypertension/adverse effects) OR 

(Drug Therapy, Combination[mh])

OR ((antihypertensive[tiab] OR anti-hypertensive[tiab]) AND (drug therapy[tiab] OR drug 

treatment[tiab] OR adverse effects[tiab] OR harm*[tiab] OR drug*[tiab] OR safety[tiab] OR 

efficacy[tiab])) OR (pharmacologic therapy[tiab] OR pharmacologic lowering of blood 

pressure[tiab])

#9 Limit to RCTs Randomized Controlled Trial[PT]

#10

Apply date 

and language 

parameters

("2010/01/01"[PDAT] : "2014/02/11"[PDAT]) AND English[lang]

2. Non-indexed Studies

Concept Search Statement

#1 Hypertension hypertension[tiab] OR hypertensive*[tiab]

#2 Outcomes (mortality[tiab] OR death*[tiab] OR morbidity[tiab] OR Cause of Death[tiab] OR Fatal 

Outcome[tiab] OR Survival Rate[tiab])

#3 (Cardiovascular Disease*[tiab] OR Coronary Disease*[tiab] OR Coronary Artery 

Disease*[tiab]) 

#4

(myocardial infarction[tiab] OR heart failure[tiab] OR stroke[tiab] OR cerebrovascular 

disorder*[tiab] OR cerebrovascular event*[tiab] OR kidney failure[tiab] OR chronic kidney 

disease*[tiab] OR CKD[tiab])

#5 Myocardial Revascularization[tiab]

#6 Creatinine[tiab]

#7 (Glomerular Filtration Rate[tiab] OR GFR[tiab] OR eGFR[tiab] OR estGFR[tiab])
October 2014 Page 93 of 135

Concept Search Statement

#8 Treatment 

((antihypertensive[tiab] OR anti-hypertensive[tiab] OR hypertension[tiab]) AND (drug 

therapy[tiab] OR drug treatment[tiab] OR adverse effects[tiab] OR harm*[tiab] OR 

drug*[tiab] OR safety[tiab] OR efficacy[tiab])) OR (pharmacologic therapy[tiab] OR 

pharmacologic lowering of blood pressure[tiab])

#9 Limit to RCTs (randomized controlled trial* [tiab] OR randomized control trial*[tiab] OR random*[tiab] OR 

single blind*[tiab] OR double blind* [tiab])

#10

Apply date 

and language 

parameters

English[lang] AND inprocess[sb]

EMBASE

Set 

# Searched for Results

S1 mesh#("Hypertension") OR emb#("Hypertension") 746211*

S2 Mesh#(“mortality”) OR Mesh#(“death”) OR Mesh#("morbidity") OR Mesh#("cause of death") OR 

Mesh#("Fatal Outcome") OR Mesh#("Survival Rate") 700514*

S3

EMB.EXACT.EXPLODE("death") OR EMB.EXACT.EXPLODE("mortality") OR 

EMB.EXACT.EXPLODE("morbidity") OR EMB.EXACT.EXPLODE("fatality") OR 

EMB.EXACT.EXPLODE("survival rate")

1304971*

S6 Mesh.exact.explode("Kidney" LNK ep) OR Mesh.exact.explode("Kidney" LNK et) OR 

Mesh.exact.explode("Kidney" LNK pp) 24150*

S7 (Mesh#(“Cardiovascular Diseases” LNK ep)) OR (Mesh#(“Cardiovascular Diseases” LNK et) ) OR 

(Mesh#(“Cardiovascular Diseases” LNK pc)) OR (Mesh#(“Cardiovascular Diseases” LNK pp)) 816897*

S9 EMB.EXACT("kidney -- epidemiology") OR EMB.EXACT("kidney -- etiology") 0°

S10 EMB.EXACT("kidney") AND EMB.EXACT.EXPLODE("pathophysiology") 11720*

S11 S6 OR S7 OR S9 OR S10 846920*

S12 EMB.EXACT.EXPLODE("chronic kidney disease") OR EMB.EXACT.EXPLODE("kidney failure") OR 

Mesh#("Renal Insuffiencieny, Chronic") 268126*

S13 S11 OR S12 1113072*

S14

Mesh#(“Myocardial revascularization”) OR mesh#(“creatinine”) OR Mesh#(“Glomerular filtration 

rate”) OR EMB#(“Heart Muscle revascularization”) OR EMB#(“Creatinine”) OR EMB#(“glomerulus 

filtration rate”)

310529*

S15

(Mesh#("Antihypertensive Agents" LNK TU)) OR (Mesh#("Antihypertensive Agents" LNK AE)) OR 

(Mesh#("Hypertension" LNK DT)) OR (Mesh#("Hypertension" LNK AE)) OR Mesh#("Drug Therapy, 

Combination")

344698*

S16

(EMB.EXACT("antihypertensive agent -- adverse drug reaction") OR EMB.EXACT("antihypertensive 

agent -- drug therapy")) OR (EMB.EXACT("hypertension -- drug therapy") OR 

EMB.EXACT("hypertension -- adverse drug reaction")) OR EMB.EXACT.EXPLODE("drug 

combination")

284864*

S17 S14 OR S15 OR S16 925541*

S18 S1 AND (S2 OR S13) AND S17 47295*

S19 S18 AND (dtype(“randomized controlled trial”) OR emb#(“randomized controlled trial”)) 4621°
October 2014 Page 94 of 135

S20 (S18 AND (dtype(“randomized controlled trial”) OR emb#(“randomized controlled trial”))) AND 

rtype.exact("Journal Article") 4070°

S21 (S18 AND (dtype(“randomized controlled trial”) OR emb#(“randomized controlled trial”))) AND 

(rtype.exact("Journal Article") AND la.exact("ENG")) 3767°

S22 (S18 AND (dtype(“randomized controlled trial”) OR emb#(“randomized controlled trial”))) AND 

(rtype.exact("Journal Article") AND la.exact("ENG") AND pd(20100101-20140212)) 575°

Cochrane CENTRAL

ID Search Hits 

#1 [mh Hypertension] or hypertension:ti,ab or hypertensiv*:ti,ab 28430

#2 [mh Mortality] or mortality:ti,ab or [mh Death] or death:ti,ab or [mh Morbidity] or morbidity:ti,ab 

or [mh "Cause of Death"] or [mh "Fatal Outcome"] or [mh "Survival Rate"] 57424

#3

([mh "Cardiovascular Diseases"/PC] or [mh "Cardiovascular Diseases"/EP] or [mh "Cardiovascular 

Diseases"/ET] or [mh "Cardiovascular Diseases"/PP] or [mh "Coronary Disease"/PC] or [mh 

"Coronary Disease"/EP] or [mh "Coronary Disease"/ET] or [mh "Coronary Disease"/PP] or [mh 

"Coronary Artery Disease"/PC] or [mh "Coronary Artery Disease"/EP] or [mh "Coronary Artery 

Disease"/ET] or [mh "Coronary Artery Disease"/PP] or [mh "Myocardial Infarction"/PC] or [mh 

"Myocardial Infarction"/EP] or [mh "Myocardial Infarction"/ET] or [mh "Myocardial Infarction"/PP] 

or [mh "Heart Failure"/PC] or [mh "Heart Failure"/EP] or [mh "Heart Failure"/ET] or [mh "Heart 

Failure"/PP] or [mh "Cerebrovascular Disorders"/PC] or [mh "Cerebrovascular Disorders"/EP] or 

[mh "Cerebrovascular Disorders"/ET] or [mh "Cerebrovascular Disorders"/PP] or [mh Stroke/PC] 

or [mh Stroke/EP] or [mh Stroke/ET] or [mh Stroke/PP] or [mh Kidney/EP] or [mh Kidney/ET] or 

[mh Kidney/PP]) 

38439

#4

(myocardial infarction:ti,ab or heart failure:ti,ab or stroke:ti,ab or "cerebrovascular disorder" 

*:ti,ab or "cerebrovascular event" *:ti,ab or "kidney failure":ti,ab or "chronic kidney disease" 

*:ti,ab or CKD:ti,ab) 

41207

#5 ([mh "Myocardial Revascularization"] or "Myocardial Revascularization":ti,ab) 8528

#6 ([mh Creatinine] or Creatinine:ti,ab) 8954

#7 ([mh "Glomerular Filtration Rate"] or "Glomerular Filtration Rate":ti,ab or GFR:ti,ab or eGFR:ti,ab 

or estGFR:ti,ab) 3783

#8

[mh "Antihypertensive Agents"/TU] or [mh "Antihypertensive Agents"/AE] or [mh 

Hypertension/DT] or [mh Hypertension/AE] or [mh "Drug Therapy, Combination"] or 

((antihypertensive:ti,ab or anti-hypertensive:ti,ab) and ("drug therapy":ti,ab or "drug 

treatment":ti,ab or "adverse effects":ti,ab or harm*:ti,ab or drug*:ti,ab or safety:ti,ab or 

efficacy:ti,ab)) or ("pharmacologic therapy":ti,ab or "pharmacologic lowering of blood 

pressure":ti,ab) 

50823

#9 #2 or #3 or #4 or #5 or #6 or #7 119748

#10 #1 and #9 and #8 8476

#11 #10 and randomized controlled trial:pt from 2010 to 2014, in Trials 881

#12 #11 not pubmed:an 426

Key Question 8

Date parameters ranged from 1966 to present.

PubMed

1. Indexed Studies

Concept Search Statement

#1 Initiation 

strategy

"Drug Therapy, Combination"[Mesh] OR "Drug Combinations"[Mesh] OR combination 

therapy[tiab] OR combined therapy[tiab] OR monotherap*[tiab] OR sequential*[tiab] OR 

step*[tiab]
October 2014 Page 95 of 135

Concept Search Statement

#2

Blood 

pressure 

treatment

"Hypertension/drug effects"[Mesh] OR "Hypertension/drug therapy"[Mesh] OR 

"Hypertension/pharmacology"[Mesh] OR "Hypertension/prevention and control"[Mesh] OR 

"Hypertension/therapeutic use"[Mesh] OR "Hypertension/therapy"[Mesh] 

#3

Blood 

pressure 

outcome

Blood Pressure[mh] OR "Hypertension"[Mesh] OR hypertens*[tiab] OR systolic 

pressure*[tiab] OR diastolic pressure*[tiab] OR arterial pressure*[tiab] OR blood pressure 

[tiab] OR BP[tiab] OR ((systol* OR diastol*) AND (pressure* OR mmHg OR mmHg)) 

#4 Limit to RCTs "Randomized Controlled Trial"[pt] 

#5

Apply date 

and language 

parameters

("1966/01/01"[PDAT] : "2014/02/20"[PDAT]) AND English[lang]

2. Non-indexed Randomized Controlled Trials

Concept Search Statement

#1 Initiation 

strategy

(drug[tiab] OR pharmacologic*[tiab]) AND (combination therapy[tiab] OR combined 

therapy[tiab] OR monotherap*[tiab] OR sequential*[tiab] OR step*[tiab] OR 

combination*[tiab])

#2

Blood 

pressure 

treatment

hypertension[tiab] AND (drug effect*[tiab] OR drug therapy[tiab] OR pharmacology[tiab] OR 

prevention[tiab] OR therapeutic use[tiab] OR therapy[tiab]) 

#3

Blood 

pressure 

outcome

hypertens*[tiab] OR systolic pressure*[tiab] OR diastolic pressure*[tiab] OR arterial 

pressure*[tiab] OR blood pressure [tiab] OR BP[tiab] OR ((systol* OR diastol*) AND 

(pressure* OR mmHg OR mmHg)) 

#4 Combine #1 AND #2 AND #3

#5 Limit to RCTs #4 AND (randomized controlled trial* [tiab] OR randomized control trial*[tiab] OR 

random*[tiab] OR single blind*[tiab] OR double blind* [tiab])

#5

Apply 

language 

limit and limit 

to studies in 

the process 

of being 

indexed

#5 AND English[lang] AND inprocess[sb]

3. Non-indexed Systematic Reviews and Meta-analyses

Concept Search Statement

#1 Initiation 

strategy

(drug[tiab] OR pharmacologic*[tiab]) AND (combination therapy[tiab] OR combined 

therapy[tiab] OR monotherap*[tiab] OR sequential*[tiab] OR step*[tiab] OR 

combination*[tiab])

#2

Blood 

pressure 

treatment

hypertension[tiab] AND (drug effect*[tiab] OR drug therapy[tiab] OR pharmacology[tiab] OR 

prevention[tiab] OR therapeutic use[tiab] OR therapy[tiab]) 

#3

Blood 

pressure 

outcome

hypertens*[tiab] OR systolic pressure*[tiab] OR diastolic pressure*[tiab] OR arterial 

pressure*[tiab] OR blood pressure [tiab] OR BP[tiab] OR ((systol* OR diastol*) AND 

(pressure* OR mmHg OR mmHg)) 

#4 Combine #1 AND #2 AND #3

#5 Limit to MAs 

and SRs #4 AND (meta-analysis[tiab] OR systematic[sb]) 
October 2014 Page 96 of 135

Concept Search Statement

#5

Apply 

language limit 

and limit to 

studies in the 

process of 

being indexed

#5 AND English[lang] AND inprocess[sb]

EMBASE

Set 

# Searched for Results

S1 Mesh#("Drug Therapy, Combination") OR Mesh#("Drug Combinations") 304057*

S2 EMB.EXACT.EXPLODE("drug combination") 190061*

S3 S1 OR S2 494118*

S4

(Mesh#("Hypertension" LNK DE)) OR (Mesh#("Hypertension" LNK TH)) OR (Mesh#("Hypertension" 

LNK TU)) OR (Mesh#("Hypertension" LNK PD)) OR (Mesh#("Hypertension" LNK DT)) OR 

(Mesh#("Hypertension" LNK PC))

80802*

S5

EMB.EXACT.EXPLODE("hypertension -- therapy") OR EMB.EXACT.EXPLODE("hypertension --

adverse drug reaction") OR EMB.EXACT.EXPLODE("hypertension -- drug therapy") OR 

EMB.EXACT.EXPLODE("hypertension -- drug administration") OR 

EMB.EXACT.EXPLODE("hypertension -- prevention")

120017*

S6 EMB#("hypertension") AND EMB#("Drug Effect") 25230*

S7 S4 OR S5 OR S6 211265*

S8 Mesh#("Blood Pressure") OR EMB.EXACT.EXPLODE("blood pressure") OR Mesh#("Hypertension") 

OR EMB#("Hypertension") 1243969*

S9 S3 AND S7 AND S8 12393*

S10 (dtype(“randomized controlled trial”) OR emb#(“randomized controlled trial”)) 727583*

S11 S9 AND S10 2156°

S12 (S9 AND S10) AND rtype.exact("Journal Article") 1826°

S13 (S9 AND S10) AND (rtype.exact("Journal Article") AND la.exact("ENG")) 1627°

S14 (S9 AND S10) AND (rtype.exact("Journal Article") AND la.exact("ENG") AND pd(19660101-

20140224)) 1627°

Cochrane CENTRAL, CDSR, DARE

ID Search Hits 

#1 [mh "Drug Therapy, Combination"] or [mh "Drug Combinations"] or "combination therapy":ti,ab 

or "combined therapy":ti,ab or monotherap*:ti,ab or sequential*:ti,ab or step*:ti,ab 66283

#2 [mh Hypertension/DT] or [mh Hypertension/PC] or [mh Hypertension/TH] or ([mh hypertension] 

and ("drug effects":ti,ab or "therapeutic use":ti,ab)) 36

#3

[mh "Blood Pressure"] or [mh Hypertension] or hypertens*:ti,ab or "systolic pressure" *:ti,ab or 

"diastolic pressure" *:ti,ab or "arterial pressure" *:ti,ab or "blood pressure" *:ti,ab or BP:ti,ab or 

((systol*:ti,ab or diastol*:ti,ab) and (pressure*:ti,ab or mmHg:ti,ab or "mmHg":ti,ab)) 

63106

#4 #1 and #2 and #3 4

#5 #4 from 1966 to 2014, in Cochrane Reviews (Reviews and Protocols), Other Reviews and Trials 4

Key Question 9
October 2014 Page 97 of 135

Date parameters ranged from 1966 to present.

A. Thiazides

PubMed Indexed Studies

Concept Search Statement

#1

Thiazide 

Treatment ("Hydrochlorothiazide"[nm] AND "Chlorthalidone"[nm]) OR ("Hydrochlorothiazide"[nm] 

AND "Indapamide"[nm]) OR ("Chlorthalidone"[nm] AND "Indapamide"[nm])

#2 Limit to RCTs "Randomized Controlled Trial"[pt] 

#3

Apply date 

and language 

parameters

("1966/01/01"[PDAT] : "2014/02/03"[PDAT]) AND English[lang]

PubMed Non-indexed Studies

Concept Search Statement

#1 Thiazide 

Treatment

("Hydrochlorothiazide"[tw] AND "Chlorthalidone"[tw]) OR ("Hydrochlorothiazide"[tw] AND 

"Indapamide"[tw]) OR ("Chlorthalidone"[tw] AND "Indapamide"[tw])

#2 Limit to RCTs randomized controlled trial* [tiab] OR randomized control trial*[tiab] OR random*[tiab] OR 

single blind*[tiab] OR double blind* [tiab]

#3

Apply date 

and language 

parameters

English[lang] AND inprocess[sb]

EMBASE

Set 

# Searched for Results

S1 Mesh#("Hydrochlorothiazide") 5839*

S2 Mesh.exact.explode("chlorthalidone") 1319°

S3 Mesh.exact.explode("indapamide") 850°

S4 (S1 AND S2) OR (S1 AND S3) OR (S2 AND S3) 281°

S5 EMB.EXACT.EXPLODE("hydrochlorothiazide") 23372*

S6 EMB.EXACT.EXPLODE("chlortalidone") 7228*

S7 EMB.EXACT.EXPLODE("indapamide") 4031°

S8 (S5 AND S6) OR (S5 AND S7) OR (S6 AND S7) 3693°

S9 S4 OR S8 3748°

S10 S9 AND (dtype(“randomized controlled trial”) OR emb#(“randomized controlled trial”)) 193°

S11 (S9 AND (dtype(“randomized controlled trial”) OR emb#(“randomized controlled trial”))) AND 

la.exact("ENG") 172°

S12 (S9 AND (dtype(“randomized controlled trial”) OR emb#(“randomized controlled trial”))) AND 

(rtype.exact("Journal Article") AND la.exact("ENG")) 43°
October 2014 Page 98 of 135

S13 (S9 AND (dtype(“randomized controlled trial”) OR emb#(“randomized controlled trial”))) AND 

la.exact("ENG") 172°

S14 (S9 AND (dtype(“randomized controlled trial”) OR emb#(“randomized controlled trial”))) AND 

(rtype.exact("Article") AND la.exact("ENG")) 77°

S15 (S9 AND (dtype(“randomized controlled trial”) OR emb#(“randomized controlled trial”))) AND 

(rtype.exact("Article") AND la.exact("ENG") AND pd(19660101-20140226)) 77°

Cochrane CENTRAL

ID Search Hits 

#1 ([mh Hydrochlorothiazide] and [mh Chlorthalidone]) or ([mh Hydrochlorothiazide] and [mh 

Indapamide]) or ([mh Chlorthalidone] and [mh Indapamide]) 69

#2 randomized controlled trial:pt 336485

#3 #1 and #2 from 1966 to 2014, in Trials 49

A. Thiazide Dose Response

1. Systematic reviews or meta-analyses with dose comparisons of any of the three thiazides of

interest.

PubMed Indexed Studies

Concept Search Statement

#1 Thiazide 

treatment

“Hydrochlorothiazide/administration and dosage"[Mesh] OR "Chlorthalidone/administration 

and dosage"[Mesh] OR "Indapamide/administration and dosage"[Mesh]

#2 "Hypertension/drug effects"[Mesh] OR "Hypertension/drug therapy"[Mesh] OR 

"Hypertension/pharmacology"[Mesh] OR "Hypertension/prevention and control"[Mesh] OR 

"Hypertension/therapeutic use"[Mesh] OR "Hypertension/therapy"[Mesh]

#3 Limit to 

systematic 

reviews

“systematic”[sb]

#4 Apply date 

and language 

parameters

("1966/01/01"[PDAT] : "2014/02/03"[PDAT]) AND English[lang]

PubMed Non-indexed Studies

Concept Search Statement

#1 Thiazide 

treatment

Hydrochlorothiazide[tw] OR Chlorthalidone[tw] OR Indapamide[tw]

#2 Hypertension[tiab] AND (drug[tiab] OR pharmacology[tiab] OR prevention[tiab] OR 

therapeutic use[tiab] OR therapy[tiab])

#3 Limit to 

systematic 

reviews

systematic[sb]

#4 Apply 

language 

parameters 

and identify 

nonindexed 

studies

English[lang] and inprocess[tsb]

Cochrane CENTRAL
October 2014 Page 99 of 135

Concept Search Statement

#1 Thiazide 

treatment

[mh Hydrochlorothiazide/AD] OR [mh Chlorthalidone/AD] OR [mh Indapamide/AD]

#2 [mh hypertension/DT] OR [mh hypertension/TH] OR [mh hypertension/PC] OR ([mh 

hypertension] AND (drug*:ti,ab OR pharmacology:ti,ab OR “therapeutic use”:ti,ab)) 

#3 Apply date 

limits

Limit to reviews databases and 1966-2014

2. RCTs with dose comparisons for indapamide as there were no relevant systematic reviews that

looked at indapamide dosage.

PubMed Indexed Studies

Concept Search Statement

#1 Thiazide 

treatment

“Indapamide/administration and dosage"[Mesh]

#2 "Hypertension/drug effects"[Mesh] OR "Hypertension/drug therapy"[Mesh] OR 

"Hypertension/pharmacology"[Mesh] OR "Hypertension/prevention and control"[Mesh] OR 

"Hypertension/therapeutic use"[Mesh] OR "Hypertension/therapy"[Mesh]

#3 Limit to RCTs "Randomized Controlled Trial"[pt] 

#4 Apply date 

and language 

parameters

("1966/01/01"[PDAT] : "2014/02/03"[PDAT]) AND English[lang]

PubMed Non-Indexed Studies

Concept Search Statement

#1 Thiazide 

treatment

Indapamide[tw]

#2 Hypertension[tiab] AND (drug[tiab] OR pharmacology[tiab] OR prevention[tiab] OR 

therapeutic use[tiab] OR therapy[tiab])

#3 Limit to RCTs randomized controlled trial* [tiab] OR randomized control trial*[tiab] OR random*[tiab] OR 

single blind*[tiab] OR double blind* [tiab]

#4 Apply 

language

parameters 

and identify 

nonindexed 

studies

English[lang] AND inprocess[sb]

Cochrane CENTRAL

Concept Search Statement

#1 Thiazide 

treatment

[mh Indapamide/AD]

#2 [mh hypertension/DT] OR [mh hypertension/TH] OR [mh hypertension/PC] OR ([mh 

hypertension] AND (drug*;ti,ab OR pharmacology:ti,ab OR “therapeutic use”:ti,ab))

#3 Limit to RCTs 

and apply 

date 

parameters

Limit to Randomized Controlled Trial:pt and 1966-2014

3. EMBASE search strategy for systematic reviews, meta-analyses, and RCTs, for three thiazide

drugs dose comparisons.
October 2014 Page 100 of 135

EMBASE

Set 

# Searched for Results

S1 (mesh#("Hydrochlorothiazide" LNK ad)) OR (mesh#("Chlorthalidone" LNK ad)) OR 

(mesh#("Indapamide" LNK ad)) 1732°

S2

EMB.EXACT.EXPLODE("hydrochlorothiazide -- drug administration") OR 

EMB.EXACT.EXPLODE("hydrochlorothiazide -- drug dose") OR 

EMB.EXACT.EXPLODE("hydrochlorothiazide -- drug concentration")

1807°

S3

EMB.EXACT.EXPLODE("Chlortalidone -- drug administration") OR 

EMB.EXACT.EXPLODE("chlortalidone-- drug dose") OR EMB.EXACT.EXPLODE("chlortalidone -- drug 

concentration")

451°

S4

EMB.EXACT.EXPLODE("Indapamide -- drug administration") OR 

EMB.EXACT.EXPLODE("indapamide-- drug dose") OR EMB.EXACT.EXPLODE("indapamide -- drug 

concentration")

408°

S5 S1 OR S2 OR S3 OR S4 3382°

S6

(Mesh#("Hypertension" LNK DE)) OR (Mesh#("Hypertension" LNK TH)) OR (Mesh#("Hypertension" 

LNK TU)) OR (Mesh#("Hypertension" LNK PD)) OR (Mesh#("Hypertension" LNK DT)) OR 

(Mesh#("Hypertension" LNK PC))

80847*

S7

EMB.EXACT.EXPLODE("hypertension -- therapy") OR EMB.EXACT.EXPLODE("hypertension --

adverse drug reaction") OR EMB.EXACT.EXPLODE("hypertension -- drug therapy") OR 

EMB.EXACT.EXPLODE("hypertension -- drug administration") OR 

EMB.EXACT.EXPLODE("hypertension -- prevention")

120142*

S8 (EMB#("hypertension") AND EMB#("Drug Effect")) OR EMB.EXACT.EXPLODE("hypertension --

pharmacology") 25256*

S9 S6 OR S7 OR S8 211452*

S10 S5 AND S9 2485°

S11 S10 AND (dtype("meta analysis") OR EMB.EXACT.EXPLODE("meta analysis") OR 

EMB.EXACT.EXPLODE("systematic review")) 90°

S12 S10 AND (dtype("review") AND AB(review n/10 (comprehensive OR system* OR method*))) 14°

S13 S11 OR S12 99°

S14 (S11 OR S12) AND la.exact("ENG") 94°

S15 S14 AND pstype("Journal") 92°

S16 S14 AND (pstype("Journal") AND fdb(10000134)) 85°

S17 S14 AND pstype("Journal") 92°

S18 S14 AND (pstype("Journal") AND la.exact("ENG")) 92°

S19 (S4 AND S9) AND pstype("Journal") 285°

S20 (S19 AND (dtype(“randomized controlled trial”) OR emb#(“randomized controlled trial”))) AND 

pstype("Journal") 73°
October 2014 Page 101 of 135

S21 (S19 AND (dtype(“randomized controlled trial”) OR emb#(“randomized controlled trial”))) AND 

(pstype("Journal") AND la.exact("ENG")) 49°

Convening the Face-to-Face Meeting

In consultation with the Contracting Officer Representative, the Champions, and the Work Group, the 

Lewin Team convened a three and a half day face-to-face meeting of the CPG Champions and Work 

Group members on April 8-11, 2014. These experts were gathered to develop and draft the clinical 

recommendations for an update to the 2004 HTN CPG. Lewin presented findings from the evidence 

review of the key questions in order to facilitate and inform the process. 

Under the direction of the Champions, the Work Group members were charged with interpreting the 

results of the evidence review, and asked to retain, revise, or reject each recommendation from the 

2004 HTN CPG. The members also developed new clinical practice recommendations, not presented in 

the 2004 HTN CPG, based on the 2014 evidence review. The subject matter experts were divided into 

two smaller subgroups at this meeting. 

Following the drafting of clinical practice recommendations, the Work Group assigned a grade for each 

recommendation based on GRADE methodology. 

Grading Recommendations

This CPG uses the GRADE methodology to assess the quality of the evidence base and assign a grade for 

the strength for each recommendation. The GRADE system uses the following four domains to assess 

the strength of each recommendation: [208] 

• Balance of desirable and undesirable outcomes

• Confidence in the quality of the evidence

• Values and preferences

• Other implications, as appropriate, e.g.,:

o Resource Use

o Equity

o Acceptability

o Feasibility

o Subgroup considerations

The following sections further describe each domain. 

Balance of desirable and undesirable outcomes refers to the size of anticipated benefits (e.g., increased 

longevity, reduction in morbid event, resolution of symptoms, improved quality of life (QoL), decreased 

resource use) and harms (e.g., decreased longevity, immediate serious complications, adverse event, 

impaired quality of life, increased resource use, inconvenience/hassle) relative to each other. This 

domain is based on the understanding that the majority of clinicians will offer patients therapeutic or 

preventive measures as long as the advantages of the intervention exceed the risks and adverse effects. 

The certainty or uncertainty of the clinician about the risk-benefit balance will greatly influence the 

strength of the recommendation.
October 2014 Page 102 of 135

Some of the discussion questions that fall under this domain include:

• Given the best estimate of typical values and preferences, are you confident that the benefits

outweigh the harms and burden or vice versa?

• Are the desirable anticipated effects large?

• Are the undesirable anticipated effects small?

• Are the desirable effects large relative to undesirable effects?

Confidence in the quality of the evidence reflects the quality of the evidence base and the certainty in 

that evidence. This second domain reflects the methodological quality of the studies for each outcome 

variable. In general, the strength of recommendation follows the level of evidence, but not always, as 

other domains may increase or decrease the strength. The evidence review used for the development of 

recommendations for the HTN CPG assessed the confidence in the quality of the evidence base and 

assigned a rate of “High,” “Moderate,” “Low” or “Very Low.” 

The elements that go into the confidence in the quality of the evidence include: 

• Is there high or moderate quality evidence that answers this question?

• What is the overall certainty of this evidence?

Values and preferences is an overarching term that includes patients’ perspectives, beliefs, 

expectations, and goals for health and life. More precisely, it refers to the processes that individuals use 

in considering the potential benefits, harms, costs, limitations, and inconvenience of the therapeutic or 

preventive measures in relation to one another. For some, the term “values” has the closest 

connotation to these processes. For others, the connotation of “preferences” best captures the notion 

of choice. In general, values and preferences increase the strength of the recommendation when there 

is high concordance and decrease it when there is great variability. In a situation in which the balance of 

benefits and risks are uncertain, eliciting the values and preferences of patients and empowering them 

and their surrogates to make decisions consistent with their goals of care becomes even more 

important. A recommendation can be described as having “similar values”, “some variation”, or “large 

variation” in typical values and preferences between patients and the larger populations of interest.

Some of the discussion questions that fall under the purview of values and preferences include:

• Are you confident about the typical values and preferences and are they similar across the

target population?

• What are the patient’s values and preferences?

• Are the assumed or identified relative values similar across the target population?

Other implications consider the practicality of the recommendation, including resources use, equity, 

acceptability, feasibility and subgroup considerations. Resource use is related to the uncertainty around 

the cost-effectiveness of a therapeutic or preventive measure. For example, statin use in the frail elderly 

and others with multiple comorbidities may not be effective and depending on the societal benchmark 
October 2014 Page 103 of 135

for willingness to pay, may not be a good use of resources. Equity, acceptability, feasibility and subgroup 

considerations require similar judgments around the practically of the recommendation.

The framework below was used by the Work Group to guide discussions on each domain. 

Table A-3. Evidence to Recommendation Framework

Decision Domain Judgment

Balance of desirable and undesirable outcomes

Given the best estimate of typical values and preferences, 

are you confident that the benefits outweigh the harms and 

burden or vice versa?

Are the desirable anticipated effects large?

Are the undesirable anticipated effects small?

Are the desirable effects large relative to undesirable 

effects?

Benefits outweigh harms/burden

Benefits slightly outweigh harms/burden

Benefits and harms/burden are balanced

Harms/burden slightly outweigh benefits

Harms/burden outweigh benefits

Confidence in the quality of the evidence

Is there high or moderate quality evidence that answers this 

question?

What is the overall certainty of this evidence?

High

Moderate

Low

Very low

Values and preferences

Are you confident about the typical values and preferences 

and are they similar across the target population?

What are the patient’s values and preferences? 

Are the assumed or identified relative values similar across 

the target population?

Similar values

Some variation

Large variation

Other implications (e.g., resource use, equity, acceptability, feasibility, subgroup considerations):

Are the resources worth the expected net benefit from the 

recommendation?

What are the costs per resource unit?

Is this intervention generally available?

Is this intervention and its effects worth withdrawing or not 

allocating resources from other interventions

Is there lots of variability in resource requirements across 

settings?

Various considerations

The strength of a recommendation is defined as the extent to which one can be confident that the 

desirable effects of an intervention outweigh its undesirable effects and is based on the framework 

above, which combines the four domains. [208] GRADE methodology does not allow for 

recommendations to be made based on expert opinion alone. While strong recommendations are 

usually based on high or moderate confidence in the estimates of effect (quality of the evidence) there 

may be instances where strong recommendations are warranted even when the quality of evidence is 

low. [209] In these types of instances where the balance of desirable and undesirable outcomes and 

values and preferences played large roles in determining the strength of a recommendation, this is 

explained in the discussion section for the recommendation. 
October 2014 Page 104 of 135

The GRADE of a recommendation is based on the following elements:

• Four decision domains used to determine the strength and direction (described above)

• Relative strength (Strong or Weak)

• Direction (For or Against)

The relative strength of the recommendation is based on a binary scale, “Strong” or “Weak.” A strong 

recommendation indicates that the Work Group is highly confident that desirable outcomes outweigh 

undesirable outcomes. If the Work Group is less confident of the balance between desirable and 

undesirable outcomes, they present a weak recommendation.

Similarly, a recommendation for a therapy or preventive measure indicates that the desirable 

consequences outweigh the undesirable consequences. A recommendation against a therapy or 

preventive measure indicates that the undesirable consequences outweigh the desirable consequences.

Using these elements, the grade of each recommendation is presented as part of a continuum:

• Strong For (or “We recommend offering this option ...”)

• Weak For (or “We suggest offering this option ...”)

• Weak Against (or “We suggest not offering this option ...”)

• Strong Against (or “We recommend against offering this option ...”)

Note that weak (For or Against) recommendations may also be termed “Conditional,” “Discretionary,” or 

“Qualified”. Recommendations may be conditional based upon patient values and preferences, the 

resources available, or the setting in which the intervention will be implemented. Recommendations 

may be at the discretion of the patient and clinician or they may be qualified with an explanation about 

the issues that would lead decisions to vary.

Drafting and Submitting the Final CPG

Following the face-to-face meeting, the Champions and Work Group members were given writing 

assignments for the update of specific sections of the 2004 HTN CPG that would form the narrative text 

for the 2014 HTN CPG. During this time, the Champions also revised the 2004 HTN algorithms and 

identified the content for the guideline summary and pocket card, as part of the provider toolkits that 

will be developed by the Office of Evidence-Based Practice, HQ MEDCOM following the publication of 

the 2014 HTN CPG. The algorithms will be included as part of this HTN CPG so as to provide a clear 

description of the flow of patient care. The final 2014 HTN CPG was submitted to the EBPWG in October

2014.
October 2014 Page 105 of 135

Appendix B: Evidence Table

2004 2014

Recommendation Grade13 Evidence14 Strength of 

Recommendation15

Screening and Diagnosis of Hypertension

Screening

1. We recommend screening adults for elevated blood pressure occur periodically,

preferably annually. (Modified from 2004 VA/DoD HTN CPG without an updated

systematic review of the evidence.)

B

Additional evidence:

[14]

Strong for

2. We suggest that screening occur at the time of routine preventive care or

routine health assessment. (Modified from 2004 VA/DoD HTN CPG without an

updated systematic review of the evidence.)

I Weak for

Diagnosis

3. We recommend the diagnosis of hypertension be determined based on at least

two blood pressure readings on two separate patient visits. (Modified from 2004

VA/DoD HTN CPG without an updated systematic review of the evidence.)

N/A

Additional evidence:

[14] 

[24]

Strong for

Measurement Techniques

4. We recommend that blood pressure be measured with a technique

recommended for the measurement of blood pressure in adults using a properly

calibrated and validated sphygmomanometer. (Modified from 2004 VA/DoD

HTN CPG without an updated systematic review of the evidence.)

A

Additional evidence:

[24] 

Strong for

13 The 2004 VA/DoD HTN CPG used the U.S. Preventive Services Task Force (USPSTF) evidence grading system. http://www.uspreventiveservicestaskforce.org 14 The evidence column indicates studies that support each recommendation. For new recommendations, developed by the 2014 guideline Work Group, the 

literature cited corresponds directly to the 2014 evidence review. For recommendations that have been carried over from the 2004 VA/DoD HTN CPG, slight 

modifications were made to the language in order to better reflect the current evidence and/or the change in grading system used for assigning the strength of 

each recommendation (USPSTF to GRADE). For these “modified” recommendations, the evidence column indicates “additional evidence,” which can refer to 

either 1) studies that support the recommendation and which were identified through the 2014 evidence review, or 2) relevant studies that support the 

recommendation, but which were not systematically identified through a literature review.

15 Refer to the Grading Recommendations section for more information on how the strength of the recommendation was determined using GRADE 

methodology.
October 2014 Page 106 of 135

2004 2014

Recommendation Grade13 Evidence14 Strength of 

Recommendation15

5. For patients whose diagnosis of hypertension remains uncertain, we

recommend offering home blood pressure monitoring to confirm diagnosis prior

to beginning pharmacologic treatment. (Two to three times a day for seven

consecutive days, disregard the first day and take the average of

measurements.)

-- [27]

[210] 

[211] 

[31] 

[30] 

Strong for

6. For patients whose diagnosis of hypertension remains uncertain, we suggest

offering 24 hour ambulatory blood pressure monitoring as an alternative to

home blood pressure monitoring to confirm diagnosis prior to beginning

pharmacologic treatment.

-- [212]

[34] 

Weak for

Adherence to Therapy

7. We suggest offering a multi-modal approach to adherence interventions, which

could include telemonitoring, multi-disciplinary group medical appointments,

(e.g., shared medical appointments), case management (by pharmacists, nurses,

social workers), patient and provider education, behavioral therapy, etc.

-- [54]

[55] 

[56] 

[57] 

[58] 

[59]

Weak for

Lifestyle Modification Therapies

8. We recommend offering lifestyle modification interventions for patients with

prehypertension or hypertension based on patient indications and preferences

as well as assessment of available local resources. (Modified from 2004 VA/DoD

HTN CPG)

A Strong for

Weight Reduction

9. We recommend discussing healthy weight range and advising overweight or

obese hypertensive patients to reduce their body mass index to below 25.

(Modified from 2004 VA/DoD HTN CPG)

B

Additional evidence:

[64] 

Strong for

10. If a normal body mass index (<25) cannot be achieved, we suggest advising

patients that a weight reduction of at least 10 pounds can achieve a decrease in

blood pressure.

-- [67]

[68] 

Weak for

Exercise/Physical Activity
October 2014 Page 107 of 135

2004 2014

Recommendation Grade13 Evidence14 Strength of 

Recommendation15

11. We recommend a target for aerobic exercise of 30 to 45 minutes per session, at

least four times per week. (Modified from 2004 VA/DoD HTN CPG)

B

Additional evidence:

[75] 

[76]

Strong for

12. We suggest the use of a self-monitoring device (e.g., pedometer, mobile apps,

etc.) to increase adherence to physical activity.

-- [73]

[74]

Weak for

Mind-body/Alternative Therapies

13. For patients interested in complementary and alternative medicine, we suggest

considering mind-body therapies such as transcendental meditation or yoga.

-- [77]

[78] 

[79]

Weak for

14. We suggest not offering Tai Chi for the treatment of hypertension as there is a

moderate body of evidence that shows this intervention does not reduce blood

pressure.

-- [80] Weak against

Dietary Modification

15. We recommend a dietitian-led Dietary Approaches to Stop Hypertension (DASH)

Diet for the treatment and/or prevention of hypertension for patients with

hypertension and/or interested patients with prehypertension and other

cardiovascular risk factors. (Modified from 2004 VA/DoD HTN CPG)

B

Additional evidence:

[213] 

Strong for

16. In patients with additional cardiovascular risk factors, such as dyslipidemia, we

suggest considering a dietitian-led Mediterranean Diet as an alternative to the

DASH Diet.

-- [85] Weak for

17. We recommend against the use of soy protein supplements for the treatment of

hypertension.

-- [88] Strong against

Sodium Reduction

18. In patients with hypertension or prehypertension, we recommend that sodium

intake be limited to no more than 2300mg/day (100mmol/day), with referral to

a dietitian or other support as appropriate. (Modified from 2004 VA/DoD HTN

CPG)

B

Additional evidence:

[90] 

[91]

Strong for
October 2014 Page 108 of 135

2004 2014

Recommendation Grade13 Evidence14 Strength of 

Recommendation15

[92]

Alcohol Reduction

19. We recommend advising hypertensive and prehypertensive patients to limit

alcohol intake to no more than 1 oz per day for men or 0.5 oz of alcohol per day

for women. (This is approximately 2 drinks/day in men and 1 drink/day in

women, where a drink is 1.5 oz 80-proof liquor, 12 oz beer, or 5 oz wine [all

14g]). (Modified from 2004 VA/DoD HTN CPG)

B

Additional evidence:

[103] 

Strong for

Pharmacological Therapy

Initiation of Pharmacotherapy

20. We recommend offering pharmacologic treatment for hypertensive patients 60

years and older with a systolic blood pressure ≥ 160 mmHg.

-- [110]

[111] 

[112]

Strong for

21. We suggest considering pharmacologic treatment using a shared decisionmaking model for hypertensive patients 60 years and older with systolic blood

pressure <160 mmHg.

-- [113] Weak for

22. We suggest offering pharmacologic treatment to patients with a history of

cerebrovascular disease (stroke, transient ischemic attack, or asymptomatic

carotid artery disease) and a systolic blood pressure ≥140 mmHg.

-- [106]

[107] 

[108] 

[109]

Weak for

23. We suggest pharmacologic treatment for hypertensive patients younger than 60

with a systolic blood pressure ≥160 mmHg, regardless of diastolic blood

pressure.

-- [114] Weak for

24. We recommend offering pharmacologic treatment for patients 30 years and

older with a diastolic blood pressure ≥90 mmHg.

-- [117]

[118] 

[111] 

[107] 

[116] 

[120] 

[121]

Strong for
October 2014 Page 109 of 135

2004 2014

Recommendation Grade13 Evidence14 Strength of 

Recommendation15

25. We suggest offering pharmacologic treatment for patients age 18 to 29 with a

diastolic blood pressure ≥90 mmHg.

-- [123]

[122] 

Weak for

Blood Pressure Goals

26. For patients 60 years and over, we recommend treating to a systolic blood

pressure goal of <150 mmHg.

-- [109]

[124] 

[110]

Strong for

27. For patients below 60 years of age, we suggest treating to a systolic blood

pressure goal of <150 mmHg.

-- [109]

[124] 

[110]

Weak for

28. We recommend treating to a diastolic blood pressure goal <90mmHg in patients

30 years and older.

-- [117]

[118] 

[120] 

[122] 

[129]

Strong for

29. We suggest treating to a diastolic blood pressure goal <90mmHg in patients age

18 to 29.

-- [117]

[118] 

[120] 

[122] 

[129]

Weak for

30. For patients with diabetes (all age groups), we recommend treating to a systolic

blood pressure goal of <150 mmHg.

-- [109]

[124] 

[131]

Strong for

31. For patients with diabetes (all age groups) who tolerate antihypertensive drugs,

we suggest treating to a systolic blood pressure goal of <140 mmHg.

-- [132] Weak for

32. For patients with diabetes, we recommend treating to a diastolic blood pressure

goal <85 mmHg.

-- [134]

[130] 

Strong for

Hypertension Control and Follow-up

33. We suggest that patients be seen within one month of initiation of lifestyle or

pharmacological therapy to determine adequacy of hypertension control,

degree of patient adherence, and presence of adverse effects. (Modified from

N/A Weak for
October 2014 Page 110 of 135

2004 2014

Recommendation Grade13 Evidence14 Strength of 

Recommendation15

2004 VA/DoD HTN CPG without an updated systematic review of the evidence.)

34. Once the patient’s blood pressure is controlled, we suggest follow-up at least

annually or more frequently as indicated, depending on patient preference.

(Modified from 2004 VA/DoD HTN CPG without an updated systematic review of

the evidence.)

N/A Weak for

Monotherapy or Combination Therapy

35. We suggest taking into consideration the patient’s baseline blood pressure and

presence of comorbidities, when deciding on either monotherapy or

combination therapy (two drugs) when initiating drug therapy. (Modified from

2004 VA/DoD HTN CPG without an updated systematic review of the evidence.)

N/A

Additional evidence:

[151] 

[152] 

[153]

Weak for

36. We suggest initiating combination therapy for patients with a baseline systolic

blood pressure of >20 mmHg or diastolic blood pressure of >10 mmHg above

the patient’s goal. (Modified from 2004 VA/DoD HTN CPG without an updated

systematic review of the evidence.)

N/A

Additional evidence:

[151] 

[152] 

[153]

Weak for

First-line Therapy

37. We recommend the use of thiazide-type diuretics for the treatment of

hypertension.

-- [151]

[154]

Strong for

38. We suggest the use of thiazide-type diuretics at recommended treatment doses

as first-line therapy for drug treatment of hypertension either as monotherapy

or in combination with other agents. (Modified from 2004 VA/DoD HTN CPG)

A

Additional evidence:

[151] 

[154]

Weak for

39. To initiate treatment of hypertension with a thiazide-type diuretic, we suggest

the use of chlorthalidone or indapamide over hydrochlorothiazide.

-- [159]

[155] 

[156] 

[157] 

[158] 

[160] 

[161]

Weak for
October 2014 Page 111 of 135

2004 2014

Recommendation Grade13 Evidence14 Strength of 

Recommendation15

40. We do not suggest switching from hydrochlorothiazide to chlorthalidone or

indapamide if the patient is adequately controlled on and tolerating

hydrochlorothiazide.

-- [163] Weak against

41. We suggest considering a switch from hydrochlorothiazide to chlorthalidone for

patients whose hypertension is inadequately controlled on 50mg/day of

hydrochlorothiazide.

-- [163] Weak for

42. We recommend a dosage of 12.5-25mg/day of chlorthalidone, 25-50mg/day of

hydrochlorothiazide, or a dosage of 2.5mg/day immediate-release or 1.5-

2.5mg/day sustained-release (not currently available in the US) of indapamide.

-- [159]

[155] 

[156] 

[157] 

[158] 

[160] 

[161]

Strong for

Alternative or Supplementary Therapies

43. We recommend using the following as alternative therapies for patients who

cannot tolerate thiazide-type diuretics, as supplementary therapies for patients

who do not reach their hypertensive goals, or for those starting on combination

therapy:

a. Angiotensin-converting-enzyme inhibitors or angiotensin II receptor

blockers (but not together)

b. Long-acting dihydropyridine calcium channel blockers

(Modified from 2004 VA/DoD HTN CPG)

A

Additional evidence:

[164] 

[166] 

Strong for

44. We recommend against the use of more than one of the following three drug

classes together in the same patient: angiotensin-converting-enzyme inhibitors,

angiotensin II receptor blockers, or direct renin inhibitors.

-- [164]

[168] 

[169] 

Strong against

45. We recommend additional therapy in refractory hypertension (for those who do

not tolerate or are not adequately controlled with triple therapy [i.e., thiazidetype diuretics, ACEI or ARB, and CCBs] described in Recommendation 43) or as

supplementary therapy in some clinical indications. Drug classes for

-- [129]

[167] 

[165] 

[170]

Strong for
October 2014 Page 112 of 135

2004 2014

Recommendation Grade13 Evidence14 Strength of 

Recommendation15

consideration can include (not in priority order):

a. Aldosterone/mineralocorticoid receptor antagonists (e.g., spironolactone,

eplerenone) 

b. Other potassium-sparing diuretic (i.e., amiloride)

c. Alpha adrenergic blockers

d. Beta adrenergic blockers

e. Non-dihydropyridine calcium channel blockers

f. Combined alpha-beta adrenergic blockers

g. Peripherally acting antiadrenergic agents (reserpine, pending availability)

h. Direct acting vasodilators (e.g., hydralazine, minoxidil)

i. Centrally acting antiadrenergic drugs (e.g., clonidine, methyldopa)

[171]

46. We recommend against the use of alpha-adrenergic blockers as monotherapy,

but this class of agents may be used as supplemental therapy or if warranted by

comorbid conditions (e.g., symptomatic prostatic hypertrophy). (Modified from

2004 VA/DoD HTN CPG)

A

Additional evidence:

[154] 

[171] 

Strong against

Specific Populations

47. In patients with hypertension and chronic kidney disease (reduced kidney

function with albuminuria), we recommend treatment with an angiotensinconverting-enzyme inhibitor, or angiotensin II receptor blocker for improving

kidney outcomes. (Modified from 2004 VA/DoD HTN CPG)

A

Additional evidence:

[176] 

[174] 

[175]

Strong for

48. In African American patients with hypertension, we recommend against using an

angiotensin-converting-enzyme inhibitor or angiotensin II receptor blocker as

monotherapy.

-- [195]

[152] 

Strong against

49. We suggest African American patients with hypertension and stage 1-3 chronic

kidney disease, we suggest a combination of a thiazide-type diuretic (for

cardiovascular protection) with either an angiotensin-converting-enzyme

inhibitor or angiotensin II receptor blocker (for renal protection).

-- [195]

[152] 

Weak for
October 2014 Page 113 of 135

Appendix C: Dietary Information 

Table D-1. Nutrient Composition of the Dietary Approaches to Stop Hypertension (DASH) Diet*[213]

Nutrient Recommended Intake

Saturated Fat 6% of total calories

Total Fat 27% of total calories

Carbohydrate 55% of total calories

Fiber 30 grams/day

Protein 18% of total calories

Cholesterol 150 mg/day

Total calories (energy)† Balance energy intake and expenditure to maintain desirable 

body weight/prevent weight gain. 

†Daily calorie expenditure should include at least 30 minutes of moderate physical activity/day. To avoid 

weight gain, the total should be approximately 60 minutes per day. 

* Additional information on the DASH diet is available at: http://www.nhlbi.nih.gov/health/healthtopics/topics/dash/. [213] 

Table D-2. Summary of Dietary Recommendations in the Mediterranean Diet* [85,214] 

Food Goal

Recommended

Olive Oil ≥ 4 tbsp. per day

Tree nuts and peanuts ≥ 3 servings per week

Fresh fruits including natural fruit juices ≥ 3 servings per day

Vegetables ≥ 2 servings per day

Seafood (primarily fatty fish) ≥ 3 servings per week

Legumes ≥ 3 servings per week

Sofrito† ≥ 2 servings per week

White Meat In place of red meat

Wine with meals ≥ 7 glasses per week, for those who drink

Discouraged

Soda drinks < 1 drink per day

Commercial baked goods, sweets, pastries‡ < 3 servings per week

Spread fats < 1 serving per day

Red and processed meats < 1 serving per day

*Dietary patterns vary both within and among countries in the Mediterranean region, precluding a

single standardized definition of the Mediterranean diet, though certain characteristic features are 

generally agreed upon by those studying its potential health effects. The table above represents the 

specific dietary recommendations used in the research study constituting our evidence base for this 

section of the guideline.

† Sofrito is a sauce made with tomato and onion, and often includes garlic, herbs, and olive oil.

‡ Commercial bakery goods, sweets, and pastries included cakes, cookies, biscuits, and custard, and did 

not include those that are homemade.
October 2014 Page 114 of 135

Appendix D: Blood Pressure Thresholds to Initiate Pharmacologic 

Therapy and Treatment Goals

Table D-1. Blood Pressure Thresholds to Initiate Pharmacologic Treatment and Treatment Goals by 

Patient Category and Age

Category of Patient

Patient 

Age

Blood 

Pressure 

(mm Hg)a 

General Population Diabetic Population

History of 

cerebrovascular 

disease

18-29 

years

Initiate SBP >160 (Suggested) >160 (Suggested)b >140 (Suggested)

DBP >90 (Suggested) >90 (Suggested)b >90 (Suggested)b

Goals 

SBP <150 (Suggested) <150 (Recommended)

<140 (Suggested for those 

who tolerate medication)

<150 (Suggested)b

DBP <90 (Suggested) <85 (Recommended) <90 (Suggested)b

30-59 

years

Initiate SBP >160 (Suggested) >160 (Suggested)b >140 (Suggested)

DBP >90 (Recommended) >90 (Recommended)b >90 (Recommended)b

Goals 

SBP <150 (Suggested) <150 (Recommended)

<140 (Suggested for those 

who tolerate medication)

<150 (Suggested)b

DBP <90 (Recommended) <85 (Recommended) <90 (Recommended)b

>60 

years

Initiate

SBP >160 (Recommended)

160 > SBP > 140 

(Suggested; using 

shared decision making)

>160 (Recommended)b

160 > SBP > 140 

(Suggested; using shared 

decision making)b

>140 (Suggested)

DBP >90 (Recommended) >90 (Recommended)b >90 (Recommended)b

Goals 

SBP <150 (Recommended) <150 (Recommended)

<140 (Suggested for those 

who tolerate medication)

<150 (Recommended)b

DBP <90 (Recommended) <85 (Recommended) <90 (Recommended)b

a Initiate pharmacologic treatment at SBP OR DBP threshold; once pharmacologic treatment is initiated, 

treat to SBP AND DBP goals.

b Evidence was not reviewed which indicated the blood pressure value should be different from the 

general population.
October 2014 Page 115 of 135

Appendix E: Drug Dosage Table

Table E-1. Recommended Dosage for Selected Hypertension Drug Therapy

Druga Usual Dose Range Commentsh

Thiazide-type Diuretics

Chlorthalidoneb 12.5-25 mg daily May cause hyperuricemia/gout.

HCTZb 12.5-50 mg dailyf Monitor K+ levels.

May cause photosensitivity (rare).

Indapamide IR: 2.5 mg daily

SRg: 1.25 – 2.5 mg daily

Angiotensin-Converting Enzyme Inhibitors

Benazepril 10-40 mg/day (daily or divided bid) When pregnancy is detected, discontinue as 

soon as possible, due to potential for fetal and 

neonatal morbidity and death. Patients of 

child-bearing potential should also be educated 

about the risks.

Do not use if history of angioedema. 

Avoid concomitant use of ACEI with ARB or 

direct renin inhibitor due to increased risk of 

hypotension, syncope, increased K+, and 

changes in renal function (See recommendation 

#44).

Monitor K+ and kidney function; use caution if 

combined with, K+ sparing diuretic, or K+ 

supplement.

Consider interruption or discontinuation in 

patients who develop clinically significant 

decline in kidney function after initiation of 

therapy, until further work-up, as indicated 

(e.g., renal artery stenosis). 

Enalapril 5-40 mg/day (daily or divided bid)

Fosinopril 10-40 mg daily

Lisinoprilb 10-40 mg daily

Ramiprilb,c 2.5-20 mg/day (daily or divided bid)

(10 mg daily for CV risk prevention)

Angiotensin II Receptor Blockers

Azilsartanc 40-80 mg daily When pregnancy is detected, discontinue as 

soon as possible. Drugs that act directly on the 

renin angiotensin system can cause injury and 

death to the developing fetus. Patients of childbearing potential should also be educated 

about the risks.

Avoid concomitant use of ACEI with angiotensin 

II receptor blocker or direct renin inhibitor due 

to increased risk of hypotension, syncope, 

increased K+, and changes in renal function (See 

recommendation #44).

Monitor K+ and kidney function; use caution if 

combined with, K+ sparing diuretic, or K+ 

supplement.

Candesartanc 8-32 mg daily

Eprosartanc 400-800 mg/daily (daily or divided bid)

Irbesartanc 150-300 mg daily

Losartanb 25-100 mg/day (daily or divided bid)

Olmesartanc 20-40 mg daily

Telmisartanc 20-80 mg daily

Valsartanb,d 80-320 mg daily
October 2014 Page 116 of 135

Consider interruption or discontinuation in 

patients who develop clinically significant 

decline in kidney function after initiation of 

therapy, until further work-up, as indicated 

(e.g., renal artery stenosis). 

Long-Acting Dihydropyridine Calcium Channel Blockers 

Amlodipineb 2.5-10 mg daily Monitor adverse effects (DHP CCBs may cause 

ankle edema, dizziness, flushing, headache).

Use with caution in patients with hepatic or 

renal dysfunction.

Felodipine 2.5-10 mg daily

Nifedipine SRb 30-120 mg daily

Aldosterone/mineralocorticoid Receptor Antagonists 

Eplerenonec 50-100 mg/day (daily or divided bid) Avoid use if hyperkalemia or severe kidney 

dysfunction.

Monitor K+ and kidney function; consider risk 

vs. benefit if combined with ACEI, ARB, K+ 

sparing diuretic, or K+ supplement.

Higher risk of gynecomastia with spironolactone 

than eplerenone.

Spironolactoneb 25-50 mg/daily

Other Potassium-Sparing Diuretics

Amiloridec 5-10 mg daily Avoid use if hyperkalemia or severe kidney 

dysfunction.

Helpful in reducing hypokalemia caused by 

thiazide diuretics.

Alpha-Adrenergic Blockers

Doxazosin 1-16 mg daily Initiate at low doses (1 mg).

Administer 1st dose at bedtime to avoid 

syncope.

Avoid use as monotherapy (See 

recommendation #46).

Prazosin 2-20 mg/day (divided bid or tid)

Terazosinb 1-20 mg daily

Beta-Adrenergic Blockers

Noncardioselective Discontinue with slow taper over one week.

Avoid combination with non-DHP CCB due to 

increased risk of bradycardia.

As doses increase, cardioselectivity decreases.

Beta-blockers should be used cautiously in 

asthma.

Propranolol IR: 80-160 mg/day (divided bid)

SR: 80-160 mg daily

Cardioselective

Atenololb 25-100 mg daily 

(adjust dose in CKD)

Metoprolol tartrateb IR: 50-300 mg/day

(daily or divided bid)

Metoprolol succinate 

(XL)b,d

SR: 25-200 mg/day

Long-Acting Non-Dihydropyridine Calcium Channel Blockers

Verapamil SRb 120-480 mg divided daily-bid Verapamil may cause constipation; verapamil is 

contraindicated in AV node dysfunction (2nd or 

3rd degree heart block), systolic HF and ↓ LV 

function.

Diltiazem SRb 120-540 mg daily Diltiazem may ↓ sinus rate and cause heart 
October 2014 Page 117 of 135

ACEI=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; AV=atrioventricular; bid=twice daily; 

CCB=calcium channel blockers; CKD=chronic kidney disease; CV=cardiovascular; DHP: dihydropyridine; 

HCTZ=hydrochlorothiazide; HF=heart failure; IR=immediate-release; K+=potassium; LV=left ventricular; SLE=systemic lupus 

erythematosus; SR=sustained-release

a

Partial list; refer to http://www.pbm.va.gov/nationalformulary.asp for items available on the VA National 

Formulary (VANF) and refer to http://pec.ha.osd.mil/formulary_search.php?submenuheader=1 for items 

available on the DoD Uniform Formulary. All drugs listed are on the DoD Uniform Formulary. b

DoD Basic Core Formulary (BCF) item. c Item not on VANF

d

Restricted to patients with chronic heart failure in VA.

e Reserpine not currently available in the U.S. due to changes in requirements for raw materials (re-verified 

10/15/2014; next available supply estimated March 2015). Refer to FDA Drug Shortages for current information. f

12.5 mg may be considered as an initial dose with titration recommended to 25 to 50mg daily; refer to 

Recommendation #42 and associated discussion for further information. g Indapamide SR not currently available in the US. h

For complete drug information, review the manufacturer’s prescribing information

block.

Use CCBs with caution in patients with liver or 

kidney dysfunction.

Combined Alpha-beta adrenergic blockers

Carvedilol IRb: 12.5-50 mg/day (divided bid)

SRc: 20-80 mg/day Precautions for beta-blockers apply.

Labetalolc 200-800 mg/day (divided bid)

Peripherally Acting Adrenergic Agents

Reserpinee 0.1-0.25 mg daily Monitor for sedation, and nasal congestion. 

Direct Acting Vasodilators

Minoxidil 2.5-100 mg/day (daily or divided bid) Direct acting vasodilators often need 

concomitant use of diuretic and beta-blocker to 

reduce edema and reflex tachycardia.

Monitor for hypertrichosis and pericardial 

effusions with minoxidil.

Monitor for headache and SLE (dose-related) 

with hydralazine.

Hydralazineb 50-200 mg/day (divided bid)

Centrally Acting Antiadrenergic Drugs

Clonidine Tabletb 0.1-0.8 mg/day (divided bid) Monitor for somnolence and dry mouth. Taper 

dose to discontinue.

Clonidine Patch 0.1-0.3 mg patch weekly Clonidine patches may be useful in select 

patients.

Methyldopa 500-2,000 mg/day (divided bid)
October 2014 Page 118 of 135

Appendix F: Participant List

James Abbott, MD

Family Medicine

Defense Health Headquarters

Falls Church, VA

Angela Allerman, PharmD, BCPS

Pharmacy

DoD Pharamcoeconomic Center

Fort Sam Houston, TX

Dan Berlowitz, MD, MPH

Geriatrics/Health Services/Quality Care

Bedford VAMC

William Cushman, MD

Preventive Medicine

Memphis VAMC

Ernest Degenhardt, COL USA (Ret.) MSN, RN, 

ANP, FNP

Chief, Office of Evidence Based Practice

Clinical Performance Directorate

US Army Medical Command

Ft. Sam Houston, TX

Corinne K.B. Devlin MSN, RN, FNP-BC

Family Nurse Practitioner

Chronic Disease Clinical Practice Guideline 

Coordinator US Army Medical Command Quality 

Management Division, Office of Evidence Based 

Practice

Elaine Furmaga, PharmD

National PBM Clinical Pharmacy Program 

Manager

VA Pharmacy Benefits Management Services

LCDR Travis Harrell, MD, FACP

Internal Medicine

Walter Reed National Medical Center

Maria O’Dowd, RN

Nursing

Walter Reed National Medical Center

Sally Peterson, RN

Nursing

St. Cloud CBOC, VA

Lillian Pinault, MS, RD, CDE

Dietitian

Baltimore VAMC

Gale H. Rutan, MD, MPH, FACP

Primary Care

Washington, DC VAMC

M. Eric Rodgers, PhD, FNP, BC

Acting Director

VA/DoD Evidence-Based CPG Program

Office of Quality, Safety and Value

Department of Veterans Affairs

Washington, DC

Pedro Roldan, MD

Primary Care

Leesburg and Clermont CBOC, Chief Medical 

Officer

CDR Robert Selvester, MD

Family Practice

Naval Air Station Corpus Christi

Corpus Christi, TX

Maj Tracy Snyder MS, RD

Dietitian

United States Air Force

Keesler AFB, MS

Addison A. Taylor, MD, PhD, FAHA 

Internal Medicine

Houston VAMC

LCDR Jacqueline Vanmoerkerque, DPT

Physical Therapy

CAPMED/Fort Belvoir Community Hospital, VA

LCDR Mark Tschanz, DO

Internal Medicine

USS Essex (LHD 2)
October 2014 Page 119 of 135

Appendix G: Acronyms List

AASK African American Study of Kidney Disease and Hypertension

ABPM Ambulatory Blood Pressure Monitoring

ACCOMPLISH Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic 

Hypertension

ACCORD Action to Control Cardiovascular Risk in Diabetes

ACEI Angiotensin-Converting-Enzyme Inhibitor

ADVANCE Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled 

Evaluation

AHA American Heart Association

AHRQ Agency for Healthcare Research and Quality

ALLHAT Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial

ANBP2 Second Australian National Blood Pressure Study

ARB Angiotensin-II Receptor Blockers

BAS Battalion Aid Station

BP Blood Pressure

BMI Body Mass Index

BUN Blood Urea Nitrogen

CABG Coronary Artery Bypass Graft

CAD Coronary Artery Disease

CBC Complete Blood Count

CBP Clinic Blood Pressure

CCB Calcium Channel Blockers

CDSR Cochrane Database of Systematic Reviews

CENTRAL Cochrane Central Register of Controlled Trials

CHD Coronary Heart Disease

CHF Chronic Heart Failure

CKD Chronic Kidney Disease

CNS Central Nervous System

COB Combined Operating Base

COR Contracting Officer’s Representative

CPG Clinical Practice Guideline

CSH Combat Support Hospital

CT Computerized Tomography

CVA Cerebrovascular Accident

CV Cardiovascular

CVD Cardiovascular Disease

DARE Database of Abstracts of Reviews of Effects

DASH Dietary Approaches to Stop Hypertension
October 2014 Page 120 of 135

DBP Diastolic Blood Pressure 

DHP Dihydropiridine

DM Diabetes Mellitus

DoD Department of Defense

DRI Direct Renin Inhibitor

EBPWG Evidence-Based Practice Working Group

ECG Electrocardiography

ESRD End Stage Renal Disease

FOB Forward Operating Base

FST Forward Surgical Team

GFR Glomular Filtration Rate

GMC Group Medical Clinic

GRADE Grading of Recommendations Assessment, Development and Evaluation

HBPM Home Blood Pressure Monitoring

HCTZ hydrochlorothiazide

HDFP Hypertension Detection and Follow-up Program

HF Heart Failure

HINTS Hypertension Intervention Nurse Telemedicine Study

HOT Hypertension Optimal Treatment Trial

HTN Hypertension

HYVET Hypertension in the Very Elderly Trial

IHD Ischemic Heart Disease

ILI Intensive Lifestyle Interventions

INSIGHT Intervention as a Goal in Hypertension Treatment trial

IOM Institute of Medicine

IR Immediate-Release

JNC7 Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, 

and Treatment of High Blood Pressure

JNC8 Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and 

Treatment of High Blood Pressure

LA Long-acting

LEARN Lifestyle Exercise Attitudes Relationships Nutrition

LSM Lifestyle Modification

LVH Left Ventricular Hypertrophy

KQ Key Question

MeSH Medical Subject Headings

MI Myocardial Infarction

MRC Medical Research Council

MRE Meals Ready to Eat

NHANES National Health and Nutrition Examination Survey
October 2014 Page 121 of 135

NHLBI National Heart, Lung, and Blood Institute

NIH National Institutes of Health

NSAID Nonsteroidal Anti-Inflammatory Drug

ONTARGET Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial

PICOTS Population, Intervention, Comparison, Outcome, Timing and Setting

PROGRESS Perindopril pROtection aGainst REcurrent Stroke Study

RAS Renin-Angiotensin System

RCT Randomized Controlled Trial

RF Risk Factors

SBP Systolic Blood Pressure

SDM Shared Decision-making

SHEP Systolic Hypertension in Elderly Patients Trial

SPRINT Systolic Blood Pressure Intervention Trial

SR Sustained-Release

Syst-Eur Systolic Hypertension in Europe Trial

TIA Transient Ischemic Attack

TMC Troop Medical Clinic

TOD Target Organ Damage

TOHP II Trials of Hypertension Prevention Phase II

TONE Trial of Nonpharmacologic Interventions in the Elderly

UA Urinalysis

US United States

USPSTF United States Preventive Services Task Force

VA Department of Veterans Affairs

VAMC Veterans Affairs Medical Center

VHA Veterans Health Administration
October 2014 Page 122 of 135

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