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March 5, 1997, Vol 277, No. 9 >
ARTICLE | March 5, 1997

Health Outcomes Associated With Antihypertensive Therapies Used as First-Line Agents: Title and subTitle BreakA Systematic Review and Meta-analysis FREE

Bruce M. Psaty, MD, PhD; Nicholas L. Smith, MPH; David S. Siscovick, MD, MPH; Thomas D. Koepsell, MD, MPH; Noel S. Weiss, MD, DrPH; Susan R. Heckbert, MD, PhD; Rozenn N. Lemaitre, PhD, MPH; Edward H. Wagner, MD, MPH; Curt D. Furberg, MD, PhD
[+] Author Affiliations

Dr Furberg has received research grants from Pfizer and Wyeth-Ayerst and in 1996 received fees for lectures sponsored by Merck and Bristol-Myers Squibb. He also serves on the Data Safety Monitoring Boards for Parke-Davis and Searle. Dr Psaty serves on the Events Committee of a clinical trial funded by Wyeth-Ayerst.

Reprints: Bruce M. Psaty, MD, PhD, Cardiovascular Health Research Unit, Suite 1360,1730 Minor Ave, Seattle, WA 98101.


JAMA. 1997;277(9):739-745. doi:10.1001/jama.1997.03540330061036
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Article
References

Objective.  —To review the scientific evidence concerning the safety and efficacy of various antihypertensive therapies used as first-line agents and evaluated in terms of major disease end points.

Data Sources.  —MEDLINE searches and previous meta-analyses for 1980 to 1995.

Data Selection.  —We selected long-term studies that assessed major disease end points as an outcome. For the meta-analysis, we chose placebo-controlled randomized trials. For randomized trials using surrogate end points such as blood pressure, we selected the largest studies that evaluated multiple drugs. Where clinical trial evidence was lacking, we relied on information from observational studies.

Data Synthesis.  —Diuretics and β-blockers have been evaluated in 18 long-term randomized trials. Compared with placebo, β-blocker therapy was effective in perventing stroke (relative risk [RR], 0.71; 95% confidence interval [CI], 0.59-0.86) and congestive heart failure (RR, 0.58; 95% CI, 0.40-0.84). The findings were similar for high-dose diuretic therapy (for stroke, RR, 0.49; 95% CI, 0.39-0.62; and for congestive heart failure, RR, 0.17; 95% Cl, 0.07-0.41). Low-dose diuretic therapy prevented not only stroke (RR, 0.66; 95% CI, 0.55-0.78) and congestive heart failure (RR, 0.58; 95% CI, 0.44-0.76) but also coronary disease (RR, 0.72; 95% CI, 0.61-0.85) and total mortality (RR, 0.90; 95% CI, 0.81-0.99). Although calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors reduce blood pressure in hypertensive patients, the clinical trial evidence in terms of health outcomes is meager. For several short-acting dihydropyridine calcium channel blockers, the available evidence suggests the possibility of harm. Whether the long-acting formulations and the nondihydropyridine calcium channel blockers are safe and prevent major cardiovascular events in patients with hypertension remains untested and therefore unknown.

Conclusion.  —Until the results of large long-term clinical trials evaluating the effects of calcium channel blockers and ACE inhibitors on cardiovascular disease incidence are completed, the available scientific evidence provides strong support for the current national guidelines, which recommend diuretics and β-blockers as firstline agents and low-dose therapy for all antihypertensive agents.

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Psaty BM, Siscovick DS, Weiss NS, et al.  Hypertension and outcomes research: from clinical trials to clinical epidemiology . Am J Hypertens . 1996;; 9:178-183.
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Figures

Tables

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure.  The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V) . Arch Intern Med . 1993;;153:154-183.
2 +
Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure.  The 1988 Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC IV) . Arch Intern Med . 1988;;148:1023-1038.
3 +
Tobian L, Brunner HR, Cohn JN, et al.  Modern strategies to prevent coronary sequelae and stroke in hypertensive patients differ from the JNC V consensus guidelines . Am J Hypertens . 1994;;7:859-872.
4 +
Manolio TA, Cutler JA, Furberg CD, Psaty BM, Whelton PK, Applegate WB.  Trends in pharmacologic management of hypertension in the United States . Arch Intern Med . 1995;;155:829-837.
5 +
Psaty BM, Siscovick DS, Weiss NS, et al.  Hypertension and outcomes research: from clinical trials to clinical epidemiology . Am J Hypertens . 1996;; 9:178-183.
6 +
Fleming TR, DeMets DL.  Surrogate end points in clinical trials: are we being misled? Ann Intern Med . 1996;;125:605-613.
7 +
MacMahon SW, Cutler JA, Furberg CD, Payne GH.  The effects of drug treatment for hypertension on morbidity and mortality from cardiovascular disease: a review of randomized controlled trials . Prog Cardiovasc Dis . 1986;;29( (suppl 1) ):99-118.
8 +
Collins R, Peto R, MacMahon S, et al.  Blood pressure, stroke, and coronary heart disease, 2: short-term reductions in blood pressure: overview of randomized drug trials in their epidemiologic context . Lancet . 1990;;335:827-838.
9 +
Mulrow CD, Cornell JA, Herrera CR, Kadri A, Farnett L, Aguilar C.  Hypertension in the elderly: implications and generalizability of randomized trials . JAMA . 1994;;272:1932-1938.
10 +
Hebert PR, Moser M, Mayer J, Glynn RJ, Hennekens CH.  Recent evidence on drug therapy of mild to moderate hypertension and decreased risk of coronary heart disease . Arch Intern Med . 1993;;153:578-581.
11 +
Cutler JA, Psaty BM, MacMahon S, Furberg CD.  Public health issues in hypertension control: what has been learned from clinical trials . In: Laragh JH, Brenner BM, eds. Hypertension: Pathophysiology, Diagnosis and Management . 2nd ed. New York, NY: Raven Press; 1995;:253-279.
12 +
Multiple Risk Factor Intervention Trial Research Group.  Multiple Risk Factor Intervention Trial: risk factor changes and mortality results . JAMA . 1982;;248:1465-1477.
13 +
Miettinen TA, Huttunen JK, Naukkarinen V, et al.  Multifactorial primary prevention of cardiovascular diseases in middle-aged men: risk factor changes, incidence and mortality . JAMA . 1985;;254:2097-2102.
14 +
Wolff FW, Lindeman RD.  Effects of treatment in hypertension: results of a controlled study . J Chronic Dis . 1966;;19:227-240.
15 +
Sprackling ME, Mitchell JRA, Short AH, Watt G.  Blood pressure reduction in the elderly: a randomised controlled trial of methyldopa . BMJ . 1981;;283:1151-1153.
16 +
The IPPPSH Collaborative Group.  Cardiovascular risk and risk factors in a randomized trial of treatment based on the beta-blocker oxprenolol: the International Prospective Primary Prevention Study in Hypertension (IPPPSH) . J Hypertens . 1985;;3:379-392.
17 +
Wilhelmsen L, Berglund G, Elmfeldt D, et al.  Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial . J Hypertens . 1987;;5:561-572.
18 +
Perry HM Jr, Goldman AI, Lavin MA, et al, for the Veterans Administration-National Heart, Lung, and Blood Institute Group for Evaluating Treatment in Mild Hypertension.  Evaluation of drug treatment in mild hypertension: VA-NHLBI feasibility study . Ann N Y Acad Sci . 1978;;304:267-288.
19 +
Veterans Administration Cooperative Study Group on Antihypertensive Agents.  Effects of treatment on morbidity in hypertension: results in patients with diastolic blood pressures averaging 115 through 129 mm Hg . JAMA . 1967;;202:116-122.
20 +
Veterans Administration Cooperative Study Group on Antihypertensive Agents.  Effects of treatment, II: results in patients with diastolic blood pressure averaging 90 through 114 mm Hg . JAMA . 1970;;213:1143-1152.
21 +
Hypertension Detection and Follow-up Program Cooperative Group.  Five-year findings of the Hypertension Detection and Follow-up Program, I: reduction in mortality of persons with high blood pressure, including mild hypertension . JAMA . 1979;;242:2562-2571.
22 +
Hypertension Detection and Follow-up Program Cooperative Group.  Five-year findings of the Hypertension Detection and Follow-up Program, III: reduction in stroke incidence among persons with high blood pressure . JAMA . 1982;;247:633-638.
23 +
Hypertension Detection and Follow-up Program Cooperative Group.  Effect of stepped care treatment on the incidence of myocardial infarction and angina pectoris: 5-year findings of the Hypertension Detection and Follow-up Program . Hypertension . 1984;;6( (suppl 1) ):I198-I206.
24 +
Hegeland A.  Treatment of mild hypertension: a five year controlled drug trial, the Oslo Study . Am J Med . 1980;;69:725-732.
25 +
The Management Committee of the Australian National Blood Pressure Study.  The Australian therapeutic trial in mild hypertension . Lancet . 1980;; 1:1262-1267.
26 +
Medical Research Council Working Party.  MRC trial of treatment of mild hypertension: principal results . BMJ . 1985;;291:97-104.
27 +
Smith WM, for the US Public Health Service Hospitals Cooperative Study Group.  Treatment of mild hypertension: results of a ten-year intervention trial . Hypertension . 1977;;25( (suppl 1) ):I98-I105.
28 +
Hypertension-Stroke Cooperative Study Group.  Effect of antihypertensive treatment on stroke recurrence . JAMA . 1974;;229:409-418.
29 +
Barraclough M, Joy MD, MacGregor GA, et al.  Control of moderately raised blood pressure: report of a co-operative randomized controlled trial . BMJ . 1973;;3:434-436.
30 +
Kuramoto K, Matsushita S, Kuwajima I, Murakami M.  Prospective study on the treatment of mild hypertension in the aged . Jpn Heart J . 1981;;22:75-85.
31 +
Carter AB.  Hypotensive therapy in stroke survivors . Lancet . 1970;;1:485-489.
32 +
Amery A, Birkenhager W, Brixko P, et al.  Mortality and morbidity from the European Working Party on high blood pressure in the elderly trial . Lancet . 1985;;1:1350-1354.
33 +
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To understand the clinical management of acute heart failure syndromes.
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