South African hypertension guideline 2011. Results of combination anti-hypertensive therapy after failure of each of the components. Department of Veterans Affairs Cooperative Study Group on Anti-hypertensive Agents. Influence of diabetes and type of hypertension on response to antihypertensive treatment. Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension. Relationship of Antihypertensive Treatment Regimens and Change in Blood Pressure to Risk for Heart Failure in Hypertensive Patients Randomly Assigned to Doxazosin or Chlorthalidone: Further Analyses from the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial A prospective evaluation of persistence on antihypertensive treatment with different antihypertensive drugs in clinical practice Management of hypertension and the core services guidelines: results from interviews with 100 Auckland general practitioners. Medical treatment of hypertension in Switzerland. The 2009 Swiss Hypertension Survey (SWISSHYPE). Genome-wide response to antihypertensive medication using home blood pressure measurements: a pilot study nested within the HOMED-BP study. Low‐dose antihypertensive therapy with 1.5 mg sustained‐ release indapamide: Results of randomised double‐blind controlled studies Comparisons of Once‐Daily Nilvadipine with Enalapril and Diuretic in Patients with Essential Hypertension Patients compliance in hypertension--the importance of number of tablets. Interaction of enalapril with sodium restriction, diuretics, and slow-channel calcium-blocking drugs. Randomised study of six beta-blockers and a thiazide diuretic in essential hypertension Differential effects of angiotensin converting enzyme inhibition and diuretic therapy on reductions in ambulatory blood pressure, left ventricular mass, and vascular hypertrophy. [The additional efficacy of the nifedipine-diuretic combination depends on the potency of the drug administered first and not the sequence of administration. A double blind study in salt-sensitive black hypertensives]. Hydrochlorothiazide is superior to isradipine for reduction of left ventricular mass: results of a multicenter trial. The Isradipine Study Group. Low-dose reserpine/thiazide combination in first-line treatment of hypertension: efficacy and safety compared to an ACE inhibitor. Effect of Spironolactone on Blood Pressure in Subjects With Resistant Hypertension A multifaceted intervention to improve blood pressure control: The Guideline Adherence for Heart Health (GLAD) study. Long‐term efficacy of a new, fixed, very‐low‐dose angiotensin‐converting enzyme‐inhibitor/diuretic combination as first‐line therapy in elderly hypertensive patients Antihypertensive efficacy and side effects of three beta‐blockers and a diuretic in elderly hypertensives: a report from the STOP‐Hypertension study
OUTCOMES Extensive data from r and omised controlled trials have shown the benefit of treating hypertension . The target blood pressure ( BP ) for antihypertensive management is systolic < 140 mmHg and diastolic < 90 mmHg with minimal or no drug side-effects ; however , stricter BP control is required for patients with end-organ damage , co-existing risk factors and co-morbidity , e.g. diabetes mellitus . The reduction of BP in the elderly and in those with severe hypertension should be achieved gradually over 1 month . Co-existent risk factors should also be controlled . BENEFITS Benefits of management include reduced risks of stroke , cardiac failure , chronic kidney disease and coronary heart disease . RECOMMENDATIONS The correct BP measurement procedure is described , and evaluation of cardiovascular risk factors and recommendations for antihypertensive therapy are stipulated . The total cardiovascular disease risk profile should be determined for all patients to inform management strategies . Lifestyle modification and patient education are cornerstones in the management of every patient . Major indications , pre caution s and contra-indications to each recommended antihypertensive drug are listed . Combination therapy should be considered ab initio if the BP is ≥ 20/10 mmHg . First-line drug therapy for uncomplicated hypertension includes low-dose thiazide-like diuretics , calcium channel blockers ( CCBs ) or angiotensin-converting enzyme inhibitors ( ACE-Is ) ( or ARBs - angiotensin II receptor blockers ) . If the target BP is not obtained , a second antihypertensive should be added from the aforementioned list . If the target BP is still not met , the third remaining antihypertensive agent should be used . In black patients  either thiazide-like diuretics or CCBs can be used initially , because response rates are better than with ACE-Is or β-blockers . In treating resistant hypertension , a central ly acting drug , vasodilator , α-blocker , spironolactone or β-locker should be added . This guideline includes management of specific situations , i.e. hypertensive emergency and urgency , severe hypertension with target organ damage , hypertension in diabetes mellitus , resistant hypertension , fixed drug combinations , new trials in hypertension , and interactions of antihypertensive agents with other drugs . VALIDITY The guideline was developed by the Southern African Hypertension Society We r and omised ambulatory men with diastolic blood pressure ( BP ) 95 - 109 mmHg without anti-hypertensive medication to single drug treatment with either  hydrochlorothiazide 12.5 - 50 mg/day , atenolol 25 - 100 mg/day , captopril 25 - 100 mg/day , clonidine 0.2 - 0.6 mg/day , diltiazem-SR 120 - 360 mg/day , prazosin 4 - 20 mg/day or placebo in a double-blind prospect i ve trial . The assigned drug was titrated to a goal BP of < 90 mm Hg . Patients not achieving goal BP were rer and omised to an alternative single active drug . Non-responders to the second drug received the first drug in combination with the second . Of the 102 non-responders to both drugs who qualified for the combination , 59 ( 57.8 % ) responded . The combination pairs that included a diuretic achieved diastolic goal BP in 69 % and < 140 mm Hg systolic in 77 % compared with 51 % and 46 % , respectively , for those combinations without a diuretic ( P = 0.067 ; P = 0.002 ) . Six of the eight terminations due to adverse drug reactions were in combinations containing prazosin ; three of these six were hypotensive reactions . We conclude that two single drugs of insufficient efficacy to control BP individually have a high probability of achieving goal BP when combined , especially if the combination contains a diuretic The aim of our investigation was to determine whether the presence of additional risk factors or type of hypertension ( diastolic or isolated systolic ) influences blood pressure ( BP ) response to treatment . The International Nifedipine GITS Study : Intervention as a Goal in Hypertension Treatment ( INSIGHT ) study is a double-blinded outcome comparison of calcium channel blockade with diuretics in high-risk patients aged 55 to 80 years . Dynamic r and omization between nifedipine once daily and hydrochlorothiazide/amiloride was performed to ensure that approximately equal numbers of patients in the 2 groups had each of the major cardiovascular risk factors . Patients with isolated systolic hypertension were also separately r and omized . Atenolol or enalapril was the m and atory second-line drug . In 5669 patients who completed the 18-week titration , BP fell from 172+/-15/99+/-9 mm Hg ( mean+/-SD ) while receiving placebo to 139+/-12/82+/-7 mm Hg . Twenty-six percent of patients required 2 drugs , and 4 % required 3 drugs . Patients with diabetes were the most resistant to treatment , requiring second and third drugs 40 % and 100 % more frequently than patients without diabetes and achieving marginally the highest final BP , for any risk group , of 141+/-13/82+/-8 mm Hg . Age , smoking , gender , hypercholesterolemia , left ventricular hypertrophy , and existing atherosclerosis had little ( < 1 mm Hg ) or no influence on BP at the end of titration , but all except smoking slightly reduced the initial response of either systolic or diastolic BP . Patients with isolated systolic hypertension were slightly more responsive than average to treatment . Our findings suggest that in patients at high absolute risk of cardiovascular complications from hypertension , the risk factors themselves do not prevent the recommended BP targets from being achieved Men aged 40 - 64 years with mild to moderate hypertension [ diastolic blood pressure ( DBP ) 100 - 130 mmHg ] were r and omized to treatment with a  diuretic ( n = 3272 ) or a  beta-blocker ( n = 3297 ) , with additional drugs if necessary , to determine whether a beta-blocker based treatment differs from thiazide diuretic based treatment with regard to the prevention of coronary heart disease ( CHD ) events and death .  Patients with previous CHD , stroke or other serious diseases , or with contraindications to diuretics or beta-blockers were excluded . If normotension ( DBP less than 95 mmHg ) was not achieved by monotherapy , other antihypertensive drugs were added , but the two basic drugs were not crossed over . Patients were assessed at 6-monthly intervals . The mean follow-up for end-points was 45.1 months . Blood pressure ( BP ) side effects and end-points were recorded in a st and ardized manner . Entry characteristics and the BP reduction achieved were very similar in both treatment groups . All analyses were made on an intention-to-treat basis . The incidence of CHD did not differ between the two treatment groups . The incidence of fatal stroke tended to be lower in the beta-blocker treated group than in the diuretic treated group . Total mortality and the total number of end-points were similar in both groups . The percentage of patients withdrawn due to side effects was similar , whereas the number of reported symptoms , according to a question naire , was higher for patients on beta-blockers . The incidence of diabetes did not differ between the two groups . Subgroup analyses did not detect a difference in the effect of beta-blockers compared with diuretics in smokers as opposed to non-smokers , and beta-blockers also had the same effects as diuretics in the quartile with the highest predicted risk for CHD . Beta-blockers and thiazide diuretics were approximately equally well tolerated . The two drugs had a similar BP reducing effect although additional drugs had to be given more often in the diuretic group . Antihypertensive treatment based on a beta-blocker or on a thiazide diuretic could not be shown to affect the prevention of hypertensive complications , including CHD , to a different extent The objective of this study was to determine which of the common groups of antihypertensive drugs is most effective at lowering systolic blood pressure ( SBP ) in elderly patients with previously untreated hypertension and the percentage of patients controlled with single or sequential monotherapy . Subjects were recruited from patients attending other outpatient clinics and entered into the study if their SBP was more than 150 mm Hg after three visits . Patients were given a low and high dose of each of the main classes of drugs or placebo for 1 month each . The study was a balanced , r and omized crossover design with five periods : placebo ; angiotensin converting enzyme inhibitors ; beta-blocking drugs ; calcium-blocking drugs ; and thiazide diuretics .  Blood pressure ( BP ) was measured 24 to 26 h after the previous dose . A question naire for side effects was administered at each visit . Seventy-four patients entered the study . beta-Blockers could not be used in 15 patients because of asthma or bronchospasm and these had two placebo periods . There were 9 of 66 patients on P , 9 of 46 on beta-blockers , 4 of 65 on calcium-blocking drugs , 4 of 65 on diuretic , and 1 of 62 patients on ACE inhibitors who did not progress to the higher dose because of side effects . Decreases in SBP compared to r and omized placebo were calcium-blocking drugs 15 mm Hg = diuretic 13 mm Hg > ACE inhibitors 8 mm Hg = beta-blockers 5 mm Hg . Blood pressure decrease correlated with placebo BP ( P < .0005 , r = 0.53 to 0.70 ) . When corrected for placebo , target SBP ( < 140 mm Hg ) was reached in between 6 % to 15 % of patients on monotherapy . Sequential monotherapy achieved target in 29 % . Angiotensin converting enzyme inhibitors , calcium-blocking drugs , and diuretics had no more side effects than placebo . Patients on beta-blockers had more side effects and the well-being score was reduced . Diuretics and calcium-blocking drugs are more effective in elderly patients at lowering SBP pressure . beta-Blockers were relatively ineffective , were frequently contraindicated , and had more side effects . Monotherapy achieved control in only a small number of patients . In elderly people with essential hypertension , therapy should be instituted with diuretics or calcium-blocking drugs , but combination therapy will usually be required to achieve goal Context Previously published results of this r and omized , double-blind trial showed that hypertensive patients treated with doxazosin rather than chlorthalidone more often developed heart failure . Did differences in blood pressure control or treatment with other drugs explain these findings ? Contribution This analysis shows that the slightly worse blood pressure control achieved with doxazosin did not explain higher risks for heart failure . Risks with doxazosin versus chlorthalidone were highest among patients who received monotherapy ( relative risk , 3.10 ) and lowest among patients who received stepped care with additional drugs ( relative risk , 1.42 ) . Implication s Increased risks for heart failure with doxazosin versus chlorthalidone are attenuated but not eliminated when additional antihypertensive drugs are used . The Editors The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial ( ALLHAT ) , a r and omized , double-blind , multicenter clinical trial including 42 418 participants at 623 clinical sites , is design ed to determine whether treatment begun with a calcium-channel blocker ( amlodipine ) , an angiotensin-converting enzyme inhibitor ( lisinopril ) , or an -adrenergic blocker ( doxazosin ) compared to treatment with a diuretic ( chlorthalidone ) reduces the incidence of fatal coronary heart disease or nonfatal myocardial infa rct ion in high-risk patients with hypertension ( 1 ) . Secondary end points are all-cause mortality , stroke , and other cardiovascular events . A lipid-lowering trial in a subset of 10 356 participants is design ed to determine whether decreasing cholesterol levels with a hydroxymethyl glutamyl coenzyme A reductase inhibitor ( pravastatin ) compared with usual care reduces all-cause mortality in older , moderately hypercholesterolemic patients . In January 2000 , the doxazosin arm of the trial was discontinued ( 2 ) because major cardiovascular disease ( relative risk , 1.25 [ 95 % CI , 1.17 to 1.33 ] ; P < 0.001 ) , especially heart failure ( relative risk , 2.04 [ 95 % CI , 1.79 to 2.32 ] ; P < 0.001 ) , was significantly increased compared with the chlorthalidone arm . Equally important , a low probability existed that doxazosin would show benefit over chlorthalidone for the primary end point by the scheduled study end , given the lack of difference ( relative risk , 1.02 [ 95 % CI , 0.90 to 1.17 ] ; P > 0.2 ] at that time . These intention-to-treat analyses compared patients assigned to chlorthalidone with patients assigned to doxazosin . In this article , we analyze how treatment changes may have affected the comparison of doxazosin with chlorthalidone in terms of heart failure . Our major objectives are to ascertain to what extent the relative risk with doxazosin versus chlorthalidone depends on 1 ) whether the assigned drugs were used as monotherapy or in combination with other agents and 2 ) the difference in decreases in systolic and diastolic blood pressure . Methods Study Design The rationale and design of ALLHAT are described in detail elsewhere ( 1 ) . In brief , eligible participants were men and women 55 years of age or older who had systolic or diastolic hypertension ( 140/90 mm Hg or hypertension controlled with medication ) plus at least one additional risk factor for coronary heart disease events . The risk factors included previous ( > 6 months ) myocardial infa rct ion or stroke , left ventricular hypertrophy on electrocardiography or echocardiography , history of type 2 diabetes , current cigarette smoking , and a low high-density lipoprotein cholesterol level . Persons with a history of hospitalized or treated symptomatic heart failure or a known ejection fraction less than 0.35 were excluded . Unless the drug regimen required tapering for safety , participants who had been taking antihypertensive medications continued to do so until the day of r and omization , at which point they stopped taking all previous medications . On the day after r and omization , treatment with the study drug was initiated . Enrollment occurred from February 1994 through January 1998 . The original reported number of 42 448 participants and 625 sites changed because 30 patients with poor documentation of informed consent were excluded ( 2 ) . Participants were assigned by a computer-generated r and omization schedule in a ratio of 1.7:1 to receive chlorthalidone or doxazosin . R and omization was stratified by center and blocked over time to maintain the ratio . All participants gave written informed consent , and all centers obtained institutional review board approval . Ascertainment of Outcomes At each clinic visit , occurrence of study end points was assessed by the clinical investigator . A hospital discharge summary was required for each hospitalized study outcome , and a death certificate was required for each death . ALLHAT defined symptomatic heart failure as clear-cut signs or symptoms of left or right ventricular dysfunction that can not be attributed to other causes . A patient had to have at least one symptom ( paroxysmal nocturnal dyspnea , dyspnea at rest , New York Heart Association class III dyspnea or other symptoms [ on less than ordinary exertion ] , or orthopnea ) and one sign ( rales , ankle edema , tachycardia , cardiomegaly or characteristic pulmonary pattern on chest radiography , S3 gallop , or jugular venous distention ) ( 3 ) . Symptoms and signs were determined by the clinic investigator through patient history , chart review , or consultation with the treating physician , but such data were not collected central ly . A one-time sample of 24 hospitalized or fatal heart failure events was review ed in a blinded manner by the ALLHAT Endpoints Subcommittee ; 20 of 24 ( 83 % ) were deemed to have complete data for a definitive diagnosis . Of the 20 cases , the agreement rate between the subcommittee and the clinic investigators was 90 % ( 18 of 20 ) and similar in both treatment groups . Details on the validity of diagnosis of heart failure will be provided in a future report . Measurement and Treatment of Blood Pressure The ALLHAT protocol specified a stepped-care treatment program for hypertension . Trained observers using st and ardized techniques measured blood pressures during the trial ( 1 , 2 ) . All blood pressures were calculated as the average of two measurements obtained with a 30-second interval between them . The blood pressure goal in all four study arms was less than 140/90 mm Hg . This level was to be achieved with the lowest possible dose of blinded first-line drug , with addition of second- and third-line open-label therapy as needed after reaching the maximal dose of first-line drug . Chlorthalidone and doxazosin were to be taken once daily in the morning . By design , doses were selected to achieve equivalent blood pressure control in the treatment groups . The first , second , and third dosage levels were 12.5 mg/d , 12.5 mg/d ( sham titration ) , and 25 mg/d , respectively , for chlorthalidone and 2 mg/d , 4 mg/d , and 8 mg/d for doxazosin . Double-blinded 1-mg and 12.5-mg doses of doxazosin and chlorthalidone , respectively , were used for the first week to minimize the frequency of postural hypotension associated with doxazosin . The identity of drugs was masked at each dosage level , but dosage level was not . After r and omization , patients were seen for dose titration as needed at 1 and 3 months per the protocol , but they could return more often until target blood pressure was reached . Subsequently , required visits occurred at 3-month intervals during the first year and at 4-month intervals thereafter . Open-label second-step drugs were added as needed and tolerated . These agents were reserpine ( 0.05 to 0.2 mg/d ) , clonidine ( 0.1 to 0.3 mg twice daily ) , and atenolol ( 25 to 100 mg/d ) . The choice of second-step drug was at the discretion of the treating clinician-investigator . The third-step agent was hydralazine ( 25 to 100 mg twice daily ) . Details of these therapies are provided elsewhere ( 1 ) . Investigators could choose to prescribe open-label antihypertensive drugs other than those provided by the study . However , use of the drug classes under study thiazide diuretics , calcium antagonists , angiotensin-converting enzyme inhibitors , and -adrenergic blockerswas strongly discouraged to avoid dilution of treatment comparisons . When clinical conditions other than uncontrolled hypertension ( for example , angina or heart failure ) were present , drugs from any study class could be used . If a step 1 drug was specifically required for blood pressure control while blinded drug treatment was continued , the step 1 drug could be added as open-label therapy but the dose could not exceed one half the maximum recommended by the Fifth Joint National Committee ( 4 ) . In most such cases , unblinding the patient or the investigator to treatment assignment was not necessary . ( Overall , < 1 % of drug identities were provided to either participant or investigator . ) Any of nine possible open-label drug typesdiuretic , calcium-channel blocker , angiotensin-converting enzyme inhibitor , -adrenergic blocker , atenolol , reserpine , clonidine , hydralazine , and other antihypertensive drug ( which could include nonatenolol -blockers , although drug name was not logged)could be recorded at each visit . Because diuretics , angiotensin-converting enzyme inhibitors , and -blockers are beneficial in preventing or treating heart failure , we call these antihypertensive heart failure drugs . Data on  antihypertensive drug use before study enrollment were collected , but not by drug class . Statistical Analysis Data were analyzed for use of additional drugs according to participants ' r and omized treatment assignments and regardless of continuation of blinded study treatment . The outcomes all heart failure ( treated outside hospital , hospitalized , or fatal ) and hospitalized or fatal heart failure were examined by treatment group for the entire cohort . The time to event for the previously published as-r and omized analyses was the interval from r and omization to first diagnosis of heart failure for patients who had an outcome , or from r and omization to Persistence on treatment affects the efficacy of antihypertensive treatment . We prospect ively investigated the persistence on therapy and the extent of  blood pressure ( BP ) control  in 347 hypertensive patients ( age 59.4 ± 6 years ) r and omly allocated to a first-line treatment with : angiotensin-converting enzyme ( ACE ) inhibitors , calcium-channel blockers ( CCBs ) , ß-blockers , angiotensin-II receptor blockers ( ARBs ) , or diuretics and followed-up for 24-months . Persistence on treatment was higher in patients treated with ARBs ( 68.5 % ) and ACE inhibitors ( 64.5 % ) vs CCBs ( 51.6 % ; p < 0.05 ) , β-blockers ( 44.8 % , p < 0.05 ) , and diuretics ( 34.4 % , p < 0.01 ) . No ARB , ACE inhibitor , β-blocker , or diuretic was associated with a higher persistence in therapy compared with the other molecules used in each therapeutic class . The rate of persistence was significantly higher in patients treated with lercanidipine vs others CCBs ( 59.3 % vs 46.6 % , p < 0.05 ) . Systolic and diastolic BP was decreased more successfully in patients treated with ARBs ( −11.2/−5.8 mmHg ) , ACE inhibitors ( −10.5/−5.1 mmHg ) , and CCBs ( −8.5/−4.6 mmHg ) compared with ß-blockers ( −4.0/−2.3 mmHg p < 0.05 ) and diuretics ( −2.3/−2.1 mmHg , p < 0.05 ) . No ARB , ACE inhibitor , β-blocker , or diuretic was associated with a higher BP control compared with the other molecules used in each therapeutic class . A trend toward a better BP control was observed in response to lercanidipine vs other CCBs ( p = 0.059 ) . The present results confirm the importance of persistence on treatment for the management of hypertension in clinical practice AIM To determine if the management of a hypothetical case of essential hypertension by general practitioners conforms with the Report to the National Advisory Committee on Core Health and Disability Services guidelines on the Management of Raised Blood Pressure in New Zeal and ( Core Services Report on Hypertension ) sent to all general practitioners in November 1992 . METHOD A cross-sectional survey of a r and om sample of 100 Auckl and general practitioners using a st and ard case of a 60 year old man with essential hypertension . Seventy interviews were conducted by a face-to-face interview and 30 by telephone interview . The main outcome measures were . Initial choice of medication and levels at which blood pressure would require treatment . RESULTS Forty one percent of the interviewed doctors had read the Core Services report on hypertension . Fifty percent of the doctors indicated they would use the recommended first line antihypertensive medication ( ie , diuretic or beta blocker ) . Doctors who prescribed beta blockers had been graduated a significantly longer time than those who did not . The majority of doctors indicated that they would initiate pharmacological treatment at lower blood pressures in younger patients than older patients contrary to the recommendation of the report . CONCLUSIONS Current reported practice is only partially consistent with that suggested by the Core Services report on hypertension . Approximately half of the doctors interviewed were prescribing the recommended first line medication . Treatment was more likely to be initiated at lower levels in younger patients than in older patients in spite of the higher absolute risk and potential absolute benefit in the latter group . Adherence to the guidelines could see a shift from overtreatment of younger patients to an increase in treatment for older patients who are at higher risk of blood pressure related disease . More specific graduate educational measures will be needed if the Core Services report on hypertension are to be implemented OBJECTIVES Despite a broad and efficient pharmacological antihypertensive armamentarium , blood pressure ( BP ) control is suboptimal and heterogeneous throughout Europe . Recent representative data from Switzerl and are limited . The goal of the present survey was therefore to assess the actual control rate of high BP in Switzerl and in accordance with current guidelines . The influence of risk factors , target organ damage and medication on BP levels and control was also evaluated . METHODS A cross-sectional visit-based survey of ambulatory hypertensive patients was performed in 2009 in Switzerl and . 281 r and omly selected physicians provided data on 5 consecutive hypertensive patients attending their practice s for BP follow-up . Data were anonymously collected on demographics , comorbidities and current medication , and BP was recorded . Subsequent modification of pharmacological antihypertensive therapy was assessed . RESULTS Data from 1376 patients were available . Mean age was 65 ± 12 years , 53.9 % were male subjects . 26.4 % had complicated hypertension . Overall , BP control ( < 140/90 mm Hg for uncomplicated and < 130/80 mm Hg for complicated hypertension ) was achieved in 48.9 % . Compared to patients with complicated hypertension , BP control was better in patients with uncomplicated hypertension ( 59.4 % vs. 19.2 % , p < 0.001 ) . As a monotherapy the most prescribed drug class were angiotensin receptor blockers ( ARB , 41 % ) , followed by angiotensin converting enzyme ( ACE ) inhibitors ( 21.5 % ) , betablockers ( 20.8 % ) and calcium channel blockers ( CCB , 10.8 % ) . The most prescribed drug combinations were ARB + diuretic ( 30.1 % ) and ACE inhibitors + diuretic ( 15.3 % ) . 46 % were receiving a fixed drug combination . In only 32.7 % of patients with uncontrolled hypertension was a change in drug therapy made . CONCLUSION This representative survey on treated adult hypertensive patients shows that , compared to earlier reports , the control rate of hypertension has improved in Switzerl and for uncomplicated but not for complicated , particularly diabetes-associated hypertension . ARBs and ACE inhibitors are the most prescribed antihypertensive drugs for monotherapy , whereas diuretics and ARBs were the most used for combination therapy BACKGROUND Patients with mild-to-moderate essential hypertension in the HOMED-BP trial were r and omly allocated to first-line treatment with a calcium channel blocker ( CCB ) , angiotensin-converting enzyme inhibitor ( ACEI ) or angiotensin II receptor blocker ( ARB ) . METHODS We recruited 265 ( 93 for CCB , 71 for ACEI and 101 for ARB ) patients who completed the genomic study .  Home blood pressure was measured for 5 days off-treatment before r and omization and for 5 days after 2 - 4 weeks of r and omized drug treatment . Genotyping was performed by 500 K DNA microarray chips . The blood pressure responses to the three drugs were analyzed separately as a quantitative trait . For replication of SNPs with p < 10(-4 ) , we used the multicenter GEANE study , in which patients were r and omized to valsartan or amlodipine . RESULTS SNPs in PICALM , TANC2 , NUMA1 and APCDD1 were found to be associated with CCB responses and those in ABCC9 and YIPF1 were found to be associated with ARB response with replication . CONCLUSION Our approach , the first based on high-fidelity phenotyping by home blood pressure measurement , might be a step in moving towards the personalized treatment of hypertension Objective In accordance with international recommendations on the need to decrease doses of antihypertensive drugs , a low-dose ( 1.5 mg ) sustained-release ( SR ) formulation of indapamide was developed to optimize the drug 's efficacy : safety ratio . The aim of this work was to evaluate the benefit of a low-dose diuretic by consolidating the efficacy and safety results of two clinical trials with a similar design . Patients and methods Clinical data were obtained in two European r and omized double-blind studies with 690 mild to moderate hypertensive patients ( 95 mmHg ≤ supine diastolic blood pressure ≤ 114 mmHg using a mercury sphygmomanometer ) treated respectively for 2 and 3 months , with a mean age of 53 and 57 years , 44 and 57 % males , mean supine diastolic blood pressure of 100.6 and 102.5 mmHg and mean supine systolic blood pressure of 161.0 and 164.5 mmHg . Results The first study , a dose-finding study with indapamide SR at 1.5 , 2 and 2.5 mg versus placebo and the immediate-release ( IR ) formulation of indapamide , showed that the 1.5 mg dosage of the new indapamide formulation had an improved antihypertensive efficacy : safety ratio . The second study confirmed the equivalence of blood pressure reductions with 1.5 mg indapamide SR and 2.5 mg indapamide IR , and better acceptability with 1.5 mg indapamide SR , particularly in the number of patients with serum potassium levels < 3.4 mmol/l , which was reduced by more than 50 % . The long-term efficacy of 1.5 mg indapamide SR was observed through a 9-month open-treatment follow-up to the second study . Conclusion The 1.5 mg SR formulation of indapamide has an improved antihypertensive efficacy : safety ratio , which is in accordance with international recommendations for the use of low-dose antihypertensive drugs and diuretics in first-line therapy of hypertension The antihypertensive efficacy of the new dihydro-pyridine derivative nilvadipine given once daily was compared in two r and omized , double-blind studies with that of hydrochlorothiazide/triamterene ( HCT/T ) and of enalapril . In the first study , arterial pressures were compared after 4 weeks of therapy with nilvadipine ( 16 mg q.d . ) or HCT/T ( 25/50 mg q.d . ) in patients with mild-to-moderate hypertension in a parallel-group design . The combination of both treatments was administered after 4 weeks if diastolic arterial pressures were < 90 mm Hg . The blood pressure ( BP ) in the nilvadipine group ( n = 125 ) was 161/102 ± 17/7 ( mean ± SD ) mm Hg after a 2-week placebo period and decreased after 4 weeks by – 16/– 13 ± 22/12 mm Hg . The BP decreased in the HCT/T group ( n = 124 ) compared to the nilvadipine group to a similar degree ( p = 0.91 , n.s . ) from 160/103 ± 17/8 mm Hg by −17/-13 ± 18/11 mm Hg . A combination therapy was started after 4 weeks in 39 patients in the nilvadipine group and in 34 patients in the HCT/T group . This led independently of the treatment sequence , to a similar decrease in BP in the nilvadipine group ( – 17/7 ± 16/10 mm Hg ) and in the HCT/T group ( -12/9 ± 16/9 mm Hg ) . In the second study , the antihypertensive effect of nilvadipine ( 1 x 8 mg ) was compared with that of enalapril ( 1x10 mg ) in a r and omized , double-blind , crossover design . Sixty-one patients with essential hypertension ( WHO I – II ) were treated over two 4-week periods following placebo periods of 2 weeks . Nonresponders ( BP < 90 mm Hg ) were subsequently treated for an additional 4 weeks with a combination of both drugs given at the same dosage . The BP decreased to a similar degree after 4 weeks on nilvadipine from 175/108 ± 13/7 mm Hg by −19/-13 mm Hg and from 176/107 ± 13/6 mm Hg by −21/-13 mm Hg after 4 weeks on enalapril to 156/95 + 14/ 9 mm Hg and 155/94 ± 16/10 mm Hg , respectively . Goal diastolic BPs < 90 mm Hg were not achieved with monotherapy in 27 patients , but 15 of these 27 patients responded favorably to a combination of nilvadipine and enalapril  with diastolic BPs < 90 mm Hg . Combination therapy caused a decrease in the diastolic BP of −14/-13 mm Hg . In conclusion , nilvadipine administered once daily was as effective as  hydrochlorothiazide or enalapril  in lowering the BP . In combination with a diuretic , the sequence of treatments , i.e. , diuretic first or nilvadipine first , had no influence on antihypertensive efficacy . The combination of calcium antagonist and diuretic was as effective as that of the calcium antagonist with enalapril The importance of number of tablets for patient compliance was investigated in 160 patients with mild-moderate essential hypertension treated with a beta-adrenoceptor blocker and a thiazide diuretic . Mean BP at entry 146 + /- 16/92 + /- 8 mm Hg . All patients were given pindolol 10 mg and clopamide 5 mg in one combination tablet or in separate tablets for 4 months respectively . Approximately 90 % of the patients took greater than 90 % of the prescribed dose throughout the study . Mean BP decreased progressively and heart rate increased slightly . Side effects were more frequently reported during the first month of the study than previously , and 30 patients discontinued the treatment . No differences in this respect were seen between 1 and 2 tablets daily . Approximately 75 % of the patients preferred 1 tablet daily , but combining two drugs in one tablet had no effect upon compliance While monotherapy sometimes controls blood pressure ( BP ) , it is often essential to add a second drug for adequate control . This study examined in a factorial fashion the interaction of enalapril with some commonly used antihypertensive therapies .  There were between 10 and 16 patients in each study , and the patients had responded in part to the two drugs used .  Enalapril and sodium restriction lowered BP 12 + /- 3/11 + /- 2 and 4 + /- 2/3 + /- 1 mm Hg , respectively . The effects of the two therapies were additive , and there was no interaction . Enalapril and hydrochlorothiazide  lowered BP 11 + /- 3/8 + /- 3 and 8 + /- 2/6 + /- 2 mm Hg , respectively . The effect of the two drugs together indicated a positive interaction of 4 + /- 2/3 + /- 1 mm Hg ( p less than 0.05 ) . Enalapril and nifedipine both lowered BP ( 10 + /- 2/8 + /- 1 and 11 + /- 3/8 + /- 1 mm Hg ) . The two drugs combined had a strongly positive interaction of 10 + /- 3/7 + /- 2 mm Hg ( p less than 0.001 ) . Enalapril can be used with the other therapeutic methods tested . If a converting enzyme inhibitor does not reduce BP adequately , it appears appropriate to add a thiazide diuretic or a slow-channel calcium-blocking drug . The mechanism of the positive interaction with diuretics probably reflects an effect on the renin-angiotensin system , but the explanation for the synergism with slow-channel calcium-blocking drugs is unclear Atenolol was compared with five other beta-blockers and a thiazide diuretic in a r and omised cross-over trial of once-daily treatment of essential hypertension .  Atenolol was significantly better at reducing resting and exercise blood pressures at 24 hours than any of the other drugs and had a low incidence of side effects . Both timolol and acebutolol had a significant hypotensive effect at 24 hours and a low incidence of side effects , suggesting that further increases in dosage might be effective and well tolerated . Labetalol proved ineffective when given once daily , and the high incidence of side effects , equalled only by pindolol , would probably prohibit further increases in dosage .  Bendrofluazide  was equal or superior to all the beta-blockers except atenolol at reducing resting blood pressure , and its cheapness still makes it an agent of first choice in mild or moderate essential hypertension Diuretic-based therapy is less effective in reducing the cardiac complications of hypertension than the risk of stroke and may be less effective in reducing left ventricular ( LV ) mass than is therapy with angiotensin converting enzyme ( ACE ) inhibition . In view of the strong association of LV hypertrophy with cardiovascular risk , this study was design ed to compare the impact of therapy with a diuretic and ACE inhibition on cardiac and vascular structure . Fifty essential hypertensives ( 74 % male , 88 % nonwhite ) participated in a double-blind study for 6 months and were r and omized to either ramipril or hydrochlorothiazide ( HCTZ ) . Echocardiography , carotid ultrasonography  , and  ambulatory blood pressure ( BP ) monitoring were performed at baseline and 3 and 6 months after initiation of therapy . The 22 ramipril patients were comparable to the 28 HCTZ patients at baseline in age , race , and 24-h BP . Although HCTZ result ed in a greater reduction in 24-h BP , only treatment with ramipril result ed in a decrease in LV mass ( 193 to 179 g , P < .005 , v 184 to 182 g , P = NS ) , attributable to a reduction in wall thicknesses but not in chamber diameter . In multivariate analysis , both change in BP and treatment group were independent predictors of change in LV mass . Importantly , although neither drug reduced carotid artery cross-sectional area , relative wall thickness increased due to a tendency for vessel diameter to decrease and wall thickness to increase , particularly in the diuretic group . Ramipril caused a sustained fall in plasma angiotensin II , whereas HCTZ increased angiotensin II levels . Although diuretic therapy was more effective in lowering ambulatory BP in this predominantly nonwhite population , only therapy with ACE inhibition was associated with regression of LV mass . Vascular geometry was altered consistent with the reduction in distending pressure result ing in vascular remodelling OBJECTIVE To evaluate whether the additional antihypertensive efficacy of the nifedipine-thiazide combination depends on the sequence of drug administration and whether the natriuretic effect of thiazide persists when co-administered with nifedipine . METHODS Double blind , r and omised , crossover , placebo-controlled study , in 12 salt-sensitive hypertensive black patients ( SSH ) . Evaluation of the antihypertensive ( 24 h ambulatory monitoring ) and natriuretic effects of placebo ( PL ) , of nifedipine-GITS ( NIF , 30 mg/d ) and of hydrochlorothiazide ( HCTZ , 25 mg/d ) given alone and in combination within two separate therapeutic sequences : PL-->NIF-->NIF + HCTZ and PL-->HCTZ-->HCTZ + NIF ( 1 month for each therapeutic regimen ) . RESULTS NIF induced greater ( p < 0.04 ) reduction of 24 h mean arterial pressure ( MAP ) ( -15.9 + /- 1.9 mm Hg , v PL ) than HCTZ ( -9.0 + /- 1.3 mm Hg ) . The association of NIF to HCTZ induced a greater ( p < 0.05 ) additional reduction of MAP-24 h ( 9.7 + /- 2.2 mm Hg ) than that produced by the association of HCTZ to NIF ( 4.1 + /- 1.3 mm Hg ) . NIF alone and in combination did not modify the diuresis-natriuresis observed with the previous treatment , whereas HCTZ alone and in combination always increased diuresis ( by 25 % ) and natriuresis ( by 53 % ) . There was a significant negative correlation ( r = -0.71 , p < 0.001 ) between blood pressure ( BP ) reduction induced by the drug administered first ( NIF or HCTZ ) and the additional BP reduction obtained by the association of the second drug . CONCLUSIONS In most of the SSH the NIF-GITS was more potent than HCTZ . NIF did not modify the diuretic-natriuretic effect of PL and of HCTZ . The greater potency of NIF may explain why in most patients the combination HCTZ to NIF induced a lower hypotensive effect than that of the association of NIF to HCTZ . Independently of the sequence of the drug administration , the lower the hypotensive effect of the drug administered first the greater the additional hypotensive effect that was observed by adding the second drug OBJECTIVES We sought to determine the efficacy of isradipine in reducing left ventricular ( LV ) mass and wall thickness in hypertensive patients . BACKGROUND LV hypertrophy on the echocardiogram is a strong predictor of cardiovascular events . Reduction of LV mass may be a desirable goal of drug therapy for hypertension . However , although thiazide diuretic drugs have been advocated as first-line therapy for hypertension , their efficacy in reducing LV mass has been question ed . METHODS Patients with mild to moderate diastolic hypertension and LV mass in excess of 1 SD of normal values were r and omized to isradipine ( n = 89 ) or hydrochlorothiazide therapy ( n = 45 ) . Evaluations were obtained at baseline , after 3 and 6 months of treatment and 2 weeks after treatment was stopped . RESULTS At 6 months , LV mass decreased by 43 + /- 45 g ( mean + /- SD ) with hydrochlorothiazide ( p < 0.001 ) but only by 11 + /- 48 g with isradipine ( p = NS ; between-group comparison , p < 0.001 ) . Two weeks after drug therapy was stopped , LV mass remained 24 + /- 41 g lower than that at baseline in the hydrochlorothiazide group ( p = 0.003 ) but only 7 + /- 50 g lower in the isradipine group ( p = NS ) . Septal and posterior wall thicknesses were significantly and equally reduced with both isradipine and hydrochlorothiazide . Greater LV mass reduction with hydrochlorothiazide was related to a 2.8 + /- 3.3-mm reduction of LV cavity size with hydrochlorothiazide but no reduction with isradipine . At 6 months of treatment , diastolic blood pressure ( BP ) by design was equally reduced in both treatment groups . At 3 months , systolic BP was reduced by 17 + /- 15 mm Hg with isradipine and by 26 + /- 15 and 25 + /- 17 mm Hg at 3 and 6 months , respectively , with hydrochlorothiazide ( p = 0.003 , between-group comparison ) . However , on stepwise multivariable regression analysis , treatment selection ( partial r2 = 0.082 , p = 0.001 ) , change in average 24-h systolic BP ( partial r2 = 0.032 , p = 0.029 ) and change in average sitting systolic BP ( partial r2 = 0.017 , p = 0.096 ) were predictive of LV mass reduction . CONCLUSIONS Despite an equivalent reduction of diastolic BP , 6 months of therapy with hydrochlorothiazide is associated with a substantial reduction of LV mass , greater than that with isradipine . The superior efficacy of hydrochlorothiazide for LV mass reduction is associated with a greater reduction of systolic BP as well as drug selection itself . These data may have important therapeutic implication The concept of initiating treatment of mild-to-moderate hypertension with a low-dose combination of reserpine and the thiazide clopamide in comparison to monotherapy with an ACE inhibitor was investigated . A total of 127 adult out patients with diastolic blood pressure between 100 and 114 mmHg were r and omized into this double-blind , parallel group study . After a 2-week wash-out period and a subsequent 2-week placebo run-in period , they were allocated to once-daily treatment with 0.1 mg reserpine plus 5 mg clopamide ( R/C ) , or 5 mg enalapril . If diastolic blood pressure was not normalized after 3 weeks of therapy ( i.e. DBP < 90 mmHg ) , the dosage was doubled from week 4 to 6 . The primary efficacy variables were the change from baseline in mean sitting diastolic and systolic blood pressure ( DBP/SBP ) after 3 weeks of therapy . Secondary variables included the change in DBP and SBP after 6 weeks of therapy , the BP normalization rates at 3 and 6 weeks and , concerning tolerability , the rates of adverse events after 6 weeks of therapy . An intent-to-treat analysis was performed . The reserpine/ clopamide and enalapril groups did not differ with regard to demographic and baseline characteristics ( mean age 57 or 58 years , respectively ; 63 % or 56 % males , respectively ; mean SBP/DBP after the 2-week placebo period = 156 mmHg/104 mmHg in both groups ) . After 3 weeks of treatment with one capsule daily , mean SBP/DBP reduction from baseline ( 24 h after last medication intake ) in the R/C combination group was -19.6/ -17.0 mmHg , in the enalapril group -6.1/ -9.5 mmHg ( between-group comparison : 2p < 0.01 for both parameters ) . The normalization rates for DBP ( < 90 mmHg ) were 64.1 % ( R/C ) and 28.6 % ( enalapril ) ( 2p < 0.01 ) . Adverse events that were considered possibly or definitely drug-related by the investigator were noted in 11 patients ( 17.2 % ) in the R/C group and in 9 patients ( 14.3 % ) in the enalapril group ( NS ) . Two patients in the enalapril group discontinued the study prematurely due to adverse events ( cough ; skin eruption ) . In the treatment of mild-to-moderate hypertension , a low-dose combination of reserpine and clopamide once a day is considerably more effective than , and as tolerable as , 5 - 10 mg of enalapril once a day . These findings suggest that treatment with a combination of different antihypertensives with different modes of action in low doses is a rational alternative to conventional monotherapy in the first-line treatment of hypertension . Besides , the " old " reserpine-diuretic regimen also in these days appears to be a rational alternative to " modern " monotherapies Spironolactone is recommended as fourth-line therapy for essential hypertension despite few supporting data for this indication . We evaluated the effect among 1411 participants in the Anglo-Sc and inavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm who received spironolactone mainly as a fourth-line antihypertensive agent for uncontrolled blood pressure and who had valid BP measurements before and during spironolactone treatment . Among those who received spironolactone , the mean age was 63 years ( SD : ±8 years ) , 77 % were men , and 40 % had diabetes .  Spironolactone was initiated a median of 3.2 years ( interquartile range : 2.0 to 4.4 years ) after r and omization and added to a mean of 2.9 ( SD : ±0.9 ) other antihypertensive drugs . The median duration of spironolactone  treatment was 1.3 years ( interquartile range : 0.6 to 2.6 years ) . The median dose of spironolactone was 25 mg ( interquartile range : 25 to 50 mg ) at both the start and end of the observation period . During spironolactone therapy , mean blood pressure fell from 156.9/85.3 mm Hg ( SD : ±18.0/11.5 mm Hg ) by 21.9/9.5 mm Hg ( 95 % CI : 20.8 to 23.0/9.0 to 10.1 mm Hg ; P<0.001 ) ; the BP reduction was largely unaffected by age , sex , smoking , and diabetic status . Spironolactone was generally well tolerated ; 6 % of participants discontinued the drug because of adverse effects . The most frequent adverse events were gynecomastia or breast discomfort and biochemical abnormalities ( principally hyperkaliemia ) , which were recorded as adverse events in 6 % and 2 % of participants , respectively . In conclusion , spironolactone  effectively lowers blood pressure in patients with hypertension uncontrolled by a mean of ≈3 other drugs . Although nonr and omized and not placebo controlled , these data support the use of spironolactone in uncontrolled hypertension BACKGROUND Although high blood pressure is associated with significant morbidity and mortality , the proportion reaching the goal blood pressures as outlined in the Seventh Report of the Joint National Committee on Prevention , Detection , Evaluation , Treatment of High Blood Pressure ( JNC 7 ) is low . We conducted a r and omized trial in primary care practice s of a multifactorial intervention targeted to improve providers ' adherence to hypertension guidelines . METHOD A total of 61 primary care practice s in North Carolina were r and omized to receive either a multifactorial intervention ( guideline dissemination via a continuing medical education session , academic detailing sessions , audit and feedback on preintervention rates of adherence , and automated blood pressure machines ) or an attention control of similar magnitude but targeted at a different guideline . Outcomes were determined through review of patient charts conducted by an independent masked quality assurance organization . RESULTS We found no difference between the 2 groups in any of the adherence measures including no difference in the percentage of patients at goal ( intervention 49.2 % , control 50.6 % ) , with undiagnosed hypertension  ( 18.1 % vs 13.6 % ) , average systolic ( 126 vs 125.1 mm Hg ) , or diastolic blood pressure ( 73.1 vs 73.4 mm Hg ) . Similarly , there was no difference in provider adherence to treatment recommendations ( use of thiazide-type diuretic as first-line therapy : 32 % vs 29.5 % ; use of 2-drug therapy in stage 2 hypertension : 11.3 % vs 10.4 % ) . CONCLUSION An intensive , multifactorial intervention did not improve adherence to national hypertension guidelines among community-based primary care . Efforts should be focused on other types of interventions to improve rates of control of hypertension Objective To determine the long-term efficacy and safety of a fixed , very-low-dose tablet combining one-half the st and ard dose of perindopril with one-quarter the st and ard dose of indapamide as first-line treatment in elderly patients . Design Double-blind , r and omized , placebo-controlled study in an outpatient setting . Patients and interventions Following a single-blind , placebo run-in period of 4 weeks , patients [ 65–85 years , with mild-to-moderate essential hypertension or isolated systolic hypertension ( ISH ) ] were r and omized to receive one tablet of perindopril 2 mg/indapamide 0.625 mg ( Per/ Ind ) ( n = 193 ) or placebo ( n = 190 ) , daily for 12 weeks . After this first 12-week period , all patients on Per/Ind ( n = 138 ) and patients responding to placebo ( n = 61 ) were maintained on their previous regimen for a further 48 weeks . Patients in the placebo group whose blood pressure was not normalized , were switched to Per/Ind ( n = 60 ) . Main outcome measure The primary endpoint was the proportion of patients with blood pressure that normalized between weeks 0 and 60 . Results After 1 year of treatment ( intention-to-treat ) supine systolic and diastolic blood pressure decreased by 23.0 ± 15.3 mmHg and 13.3 ± 9.4 mmHg with Per/Ind ( n = 253 : 193 from r and omized Per/Ind group and 60 from the placebo group switched at week 12 ) . The mean decreases in systolic blood pressure were similar in essential hypertension and ISH ( systolic blood pressure 23.2 versus 22.7 mmHg , respectively ) . Per/Ind treatment ( n = 253 ) achieved an initial normalization of blood pressure in 96.2 % [ 95 % confidence interval ( CI ) 93.6–98.9 % ; Kaplan-Meier estimate ] of Per/Ind-treated patients ; 79.8 % ( 95 % CI 74.1–85.5 % ) of these maintained a normalized blood pressure throughout the 1-year follow-up . The incidence of adverse events was similarly low in the placebo and active therapy groups . Efficacy and safety results for the over 75 years subgroup were similar to those for the younger elderly subjects Conclusions The fixed , very low-dose combination of perindopril 2 mg/indapamide 0.625 mg results in sustained blood pressure control when used as first line treatment of elderly hypertensive patients over 1-year , and is well-tolerated Objective : To compare the blood pressure‐lowering efficacy , the frequency of side effects and changes in laboratory values of three & bgr;‐blockers and a potassium‐sparing diuretic combination in elderly hypertensive patients . Design : The Swedish Trial in Old Patients with Hypertension ( STOP‐Hypertension ) was a prospect i ve , r and omized , double‐blind , multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70‐84 years . Methods : The study group consisted of 1627 elderly hypertensive patients ( mean ± SD age 75.7 ± 3.7 years ; 37 % males , 63 % females ) . Supine and st and ing blood pressure , heart rate and side effects were recorded at each visit . Blood was drawn for routine analysis . The mean length of follow‐up was 25 months ( range 6‐65 ) . No patient was lost to follow‐up . Results : After 2‐months ' single‐drug therapy , all four active drugs were found to be equally effective in reducing diastolic blood pressure ( DBP ) . However , there were differences in their efficacy in reducing systolic blood pressure ( SBP ) ; the diuretic was significantly more effective than the & bgr;‐receptor blockers . The results of a series of multiple linear regression analyses showed that the observed differences in effect on SBP could not be explained by the different effects of the drugs on heart rate . More than two‐thirds of the patients were given supplementary treatment , most of them already by the 2‐month visit , after which there was no significant difference in blood pressure among the treatment regimens . The changes in laboratory values and in the prevalence of symptoms were minor for all four regimens . Conclusion : Metoprolol ( controlled release ) , atenolol , pindolol and the combination hydrochlorothiazide + amiloride were equally effective as single drugs in reducing DBP . There were differences in their efficacy in reducing SBP , the diuretic being more effective than the & bgr;‐blockers . After addition of supplementary treatment ( & bgr;‐blocker to diuretic , or vice versa ) there were no significant differences in blood pressure reduction among the groups . The changes in laboratory values and in the prevalence of symptoms were minor for all active treatment regimens . Thus , the satisfactory effect on cardiovascular morbidity and mortality was not impaired by low tolerability of the drugs
The effect was similar to that obtained when thiazides are used as a single agent .
Thiazides when given as a second-line drug have a dose related effect to lower blood pressure that is similar to when they are added as a first-line drug .
This means that the BP lowering effect of thiazides is additive .
Loop diuretics appear to have a similar blood pressure lowering effect as thiazides at 1 times the recommended starting dose .
Because of the short duration of the trials and lack of reporting of adverse events , this review does not provide a good estimate of the incidence of adverse effects of diuretics given as a second-line drug
BACKGROUND Diuretics are widely prescribed for hypertension not only as a first-line drug but also as a second-line drug .
Therefore , it is essential to determine the effects of diuretics on blood pressure ( BP ) , heart rate and withdrawals due to adverse effects ( WDAEs ) when given as a second-line drug .