***Evidence Report/Technology Assessment***

**Number 80**

**Results of Systematic Review of Research on Diagnosis and Treatment of Coronary Heart Disease in Women**

**Prepared for:**

Agency for Healthcare Research and Quality

U.S. Department of Health and Human Services

www.ahrq.gov

**Contract No. 290-97-0013**

**Prepared by**:

###### University of California, San Francisco-Stanford University Evidence-based Practice Center, Stanford, CA

*Principal Investigator*

Deborah Grady, MD, MPH 

*EPC Coordinator*

Kathryn McDonald, MM

*EPC Staff*

Kara Bischoff

Aurelie Cabou

Lily Chaput, MD, MPH

Kate Hoerster

Margaret Kristof, MS, RN

Cyrus Shahpar, MPH

Judith Walsh, MD, MPH

*UCSF/Mt. Zion Fishbon Librarians*

Gail Sorrough, MLIS

Gloria Won, MLIS

**AHRQ Publication No. 03-E035**

**May 2003**

 SEQ CHAPTER \h \r 1This document is in the public domain and may be used and reprinted without permission except those copyrighted materials noted for which further reproduction is prohibited without the specific permission of copyright holders.

**Suggested Citation:**

Grady D, Chaput L, Kristof  M. Results of Systematic Review of Research on Diagnosis and Treatment of Coronary Heart Disease in Women.  Evidence Report/Technology Assessment 

No. 80. (Prepared by the University of California, San Francisco-Stanford Evidence-based Practice Center under Contract No 290-97-0013.) AHRQ Publication No. 03-0035. Rockville, MD: Agency for Healthcare Research and Quality. May 2003.

 SEQ CHAPTER \h \r 1**Preface**

The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-Based Practice Centers (EPCs), sponsors the development of evidence reports and technology assessments to assist public- and private-sector organizations in their efforts to improve the quality of health care in the United States.  The reports and assessments provide organizations with comprehensive, science-based information on common, costly medical conditions and new health care technologies.  The EPCs systematically review the relevant scientific literature on topics assigned to them by AHRQ and conduct additional analyses when appropriate prior to developing their reports and assessments.

To bring the broadest range of experts into the development of evidence reports and health technology assessments, AHRQ encourages the EPCs to form partnerships and enter into collaborations with other medical and research organizations.  The EPCs work with these partner organizations to ensure that the evidence reports and technology assessments they produce will become building blocks for health care quality improvement projects throughout the Nation.  The reports undergo peer review prior to their release.  

AHRQ expects that the EPC evidence reports and technology assessments will inform individual health plans, providers, and purchasers as well as the health care system as a whole by providing important information to help improve health care quality.

We welcome written comments on this evidence report.  They may be sent to: Director, Center for Practice and Technology Assessment, Agency for Healthcare Research and Quality, 6010 Executive Blvd., Suite 300, Rockville, MD 20852.

Carolyn M. Clancy, M.D.

Director

Agency for Healthcare Research and Quality

## Structured Abstract 

# Objectives.  The Agency for Healthcare Research and Quality and several partner organizations charged the University of California, San Francisco-Stanford Evidence-based Practice Center to review the evidence on five key topics related to coronary heart disease (CHD) in women: (1) accuracy of noninvasive testing for diagnosis of CHD; (2) efficacy of  treatments; (3) strength of risk factors and efficacy of risk factor reduction; (4) utilization of tests and treatments in men compared to women, and (5) accuracy of biomarkers for diagnosis of myocardial infarction. These five key questions included 42 discrete subtopics. We used standard methods to systematically review the medical literature to address each subtopic. The evidence identified was reviewed, graded and summarized for each subtopic and further research was recommended as appropriate.

**Search Strategy.**  We identified 6,403 citations from searching electronic databases from 1985 through July 2001, reviewing bibliographies, and by recommendation from our peer reviewers. 

# Selection Criteria.  After the titles were screened, abstracts were reviewed independently by two investigators who coded each abstract for eligibility for full text review.  In order to be categorized as providing evidence regarding a research question, the article had to address the predictor variable and the clinical outcome and contain data to address the question specifically in women. Articles meeting inclusion criteria were abstracted independently on a standardized form by two investigators, and received a quality score based on predefined criteria.  All studies rated good or fair were included in this review.

# Data Collection and Analysis.  The titles and abstracts were entered and coded in EndNote® files. Data from the standardized review form was entered into a Microsoft® Access database, which allowed tracking of the eligibility, quality and type of study of each article reviewed.

# Main Results.  We reviewed the full text of 819 articles and found 162 that provided evidence in women. We found no data in women to address 13 of the subtopics, weak data to address 15, fair data for eight and good data to address six. 

· Fair evidence suggests that the accuracy of exercise EKG and exercise thallium testing for CHD in women is low. The accuracy of exercise echocardiography appears to be higher, but data are limited.

· Fair or good evidence suggests that beta-blockers, aspirin and angiotensin converting enzyme inhibitors reduce risk for CHD events and that nitrates are ineffective  in women with known heart disease. 

· Fair evidence suggests that glycoprotein IIb/IIIa inhibitor drugs given to women undergoing percutaneous revascularization  result in a reduced risk of CHD events and need for revascularization, but treatment of women suffering acute coronary syndromes may result in increased mortality. This was the only treatment for which there was evidence of a possible interaction by gender: men treated with IIb/IIIa drugs during acute coronary syndromes appear to benefit.

· Fair or good evidence suggests that hyperlipidemia, diabetes, and hyperhomocysteinemia are risk factors for CHD in women. 

· Fair or good evidence suggests that smoking cessation after MI and treatment of hypertension and hyperlipidemia lower risk for CHD events in women.

· We found little evidence to address the key questions in women of different races or ethnicities. The only evidence regarding differences by ethnicity suggests that African- American women may benefit more from treatment of hypertension than white women.

**Conclusions.**New or updated systematic reviews of the literature appear to be feasible and would likely provide clinically important information for 14 of the subtopics. The major limitation in performing these systematic reviews is that data stratified by gender and race/ethnicity from completed studies may not available. We recommend that, in addition to requiring participation of women and minorities in research, the National Institutes of Health, U.S. Food and Drug Administration and other funding and regulatory agencies insist that outcome data by subgroup be published or archived. 

# Contents

Summary1

**Evidence Report**9

Chapter 1.  Introduction 11

Coronary Heart Disease in Women11

Approaches to Improving Evidence on Diagnosis and Treatment of CHD in Women12

Key Questions12

Chapter 2.  Methodology17

Identification of Evidence17

Data Sources17Search Terms17

Inclusion Criteria15

Article Identification18

Quality Assessment18

Completeness19

Data Management and Archive20

Results of Literature Searches20

Summary of Evidence21

Hierarchy of Evidence and Completeness of Searches21

Summary of Studies22

Evidence by Ethnicity23

Abbreviations23

Chapter 3. Results 27

Results by Key Question27

Question 1: Are there accurate non-invasive approaches to evaluating suspected 

coronary disease in women?27                                      

Question 2: Are there effective treatments for women with coronary heart disease?34

Question 3: What are the risk factors for coronary heart disease in women? Does 

modifying these risk factors result in reduced events, and what are the most 

effective methods for modifying these risk factors?63

Question 4: Are accurate tests, effective treatments, or risk factor modifications underutilized in women compared to men or among women of various 

race/ethnic populations?93

Question 5: What is the prognostic value of biochemical markers for acute 

myocardial infarction or unstable angina in women?102

Chapter 4. Conclusions103

Summary and Recommendations by Key Question103

Findings by Level of Evidence and Key Question103

Summary of Major Findings103

Chapter 5.  Future Research115

**Figures**

Figure 1. Process for Identification of Evidence24

**Tables**

Table 1.   List of Key Questions14  

Table 2.   Articles Identified by Key Question and Topic25

Table 3.   Summary and Recommendations by Key Question105

Table 4.   Findings by Level of Evidence and Key Question113

Table 5.   Findings by Level of Evidence and Recommendation for Systematic Review116

References117

Evidence Tables125

Table 1. Articles Containing Evidence on Key Questions127

Bibliography143

Appendixes177

Appendix A.  Technical Expert Advisory Board and Expert Consultants181 

Appendix B.  Literature Search Terms185

Appendix C.  Full-Text Article Abstraction Form191

Appendix D.  Articles Eligible for Full Text Review by Key Question195

Appendix E.  Cost-effectiveness Analyses253

Appendix F.  Clinical Practice Guidelines257

Appendix G.  Evidence Reports263

Appendix H.  Abbreviations and Acronyms 267

� SEQ CHAPTER \h \r 1�This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or a basis for reimbursement and coverage policies.  AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

AHRQ is the lead Federal agency charged with supporting research designed to improve the quality of health care, reduce its cost, address patient safety and medical errors, and broaden access to essential services. AHRQ sponsors and conducts research that provides evidence-based information on health care outcomes; quality; and cost, use, and access. The information helps health care decisionmakers—patients and clinicians, health system leaders, and policymakers—make more informed decisions and improve the quality of health care services.

Jean Slutsky, P.A., M.S.P.H.

Acting Director, Center for Practice and                                        Technology Assessment

Agency for Healthcare Research and Quality

� SEQ CHAPTER \h \r 1�The authors of this report are responsible for its content.  Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services of a particular drug, device, test, treatment, or other clinical service.

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