Advertisement

Review of the long-term controlled trials of usefulness of therapy for systemic hypertension

  • Ray W. Gifford Jr.
    Correspondence
    Address for reprints: Ray W. Gifford, Jr., MD, Department of Hypertension and Nephrology, Desk A-101, The Cleveland Clinic Foundation, One Clinic Center, 9500 Euclid Avenue, Cleveland, Ohio 44195-5042.
    Affiliations
    From the Division of Medicine and the Department of Hypertension and Nephrology, The Cleveland Clinic Foundation, Cleveland, Ohio U.S.A.
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      A number of long-term clinical trials involving over 40,000 patients have been performed to study the effectiveness of antihypertensive therapy in controlling high blood pressure and in reducing the morbidity and mortality associated with hypertension. Only diuretics and β blockers have been studied in long-term trials to determine their efficacy in reducing cardiovascular morbidity and mortality. The Hypertension Detection and Follow-Up Program (HDFP), Medical Research Council (MRC) trial, European Working Party on Hypertension in the Elderly (EWPHE) trial, Australian Therapeutic Trial in Mild Hypertension, and the Veterans Administration Cooperative Study all showed a reduction in stroke rate. The EWPHE and HDFP trials were the only studies to show a statistically significant reduction in mortality from myocardial infarction. All of these were diuretic-based; in addition, the MRC trial also used a β blocker as first-step therapy in 1 cohort.
      The International Primary Prospective Prevention Study in Hypertension and Heart Attack Primary Prevention in Hypertension (HAPPHY) trials compared β-blocker and non-β-blocker or diuretic-based therapies and found no significant difference between the treatment groups in the incidence of stroke or cardiac events. Neither study had a control group, so it was impossible to determine if there was any reduction in stroke or cardiac events.
      The Metoprolol Atherosclerosis Prevention in Hypertension trial, an extension of the HAPPHY trial, showed that smokers receiving the β blocker metoprolol had a significantly lower cardiovascular mortality rate than those randomized to a diuretic drug. However, subgroup analysis of the HAPPHY data showed no difference in the effect of β blockers and diuretics in smokers.
      The Multiple Risk Factor Intervention Trial had an unexpected result: Hypertensive men with electrocardiographic abnormalities at rest who were treated with diuretic drugs in the special intervention group had a higher mortality rate than similar men in the usual-care group. It has been suggested that this was due to arrhythmias from diuretic-induced hypokalemia, but the data do not support this hypothesis.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Hypertension Detection and Follow-up Program Cooperative Group
        The effect of treatment on mortality in “mild” hypertension: results of the Hypertension Detection and Follow-up Program.
        N Engl J Med. 1982; 307: 976-980
        • 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
        • Hypertension Detection and Follow-up Program Cooperative Group
        Five-year findings of the Hypertension Detection and Follow-up Program: II. Mortality by race-sex and age.
        JAMA. 1979; 242: 2572-2577
        • Hypertension Detection and Follow-Up Program Cooperative Group
        Persistence of reduction in blood pressure and mortality of participants in the Hypertension Detection and Follow-up Program.
        JAMA. 1988; 259: 2113-2122
        • Medical Research Council Working Party
        MRC trial of treatment of mild hypertension: principal results.
        Br Med J. 1985; 291: 97-102
        • Greenberg G
        • Thompson SG
        • Brennan PJ
        The relationship between smoking and the response to antihypertensive treatment in mild hypertensives in the Medical Research Council's trial of treatment.
        Int J Epidemiol. 1987; 16: 25-30
        • Amery A
        • Brixko P
        • Clement D
        • De Schaepdryver A
        • Fagard R
        • Forte J
        • Henry JF
        • Leonetti G
        • O'Malley K
        • Strasser T
        • Birkenhäger W
        • Bulpitt C
        • Deruyttere M
        • Dollery C
        • Forette F
        • Hamdy R
        • Joossens JV
        • Lund-Johansen P
        • Petrie J
        • Tuomilehto J
        • Williams B
        Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly Trial.
        Lancet. 1985; 1: 1349-1354
      1. Lancet. 1980; 1: 1261-1267
        • 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
        • Freis ED
        The Veterans Adminstration Cooperative Study on Antihypertensive Agents. Implications for stroke prevention.
        Stroke. 1974; 5: 76-77
        • 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
        • The Heart Attack Primary Prevention in Hypertension Trial Research Group
        Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial.
        J Hypertens. 1987; 5: 561-572
        • Wikstrand J
        • Warnold I
        • Olsson G
        • Tuomilehto J
        • Elmfeldt D
        • Berglund G
        • On behalf of the Advisory Committee
        Primary prevention with metoprolol in patients with hypertension: mortality results from the MAPHY study.
        JAMA. 1988; 259: 1976-1982
        • Multiple Risk Factor Intervention Trial Research Group
        Multiple Risk Factor Intervention Trial: risk factor changes and mortality results.
        JAMA. 1982; 248: 1465-1477
        • Multiple Risk Factor Intervention Trial Research Group
        Baseline rest electrocardiographic abnormalities, antihypertensive treatment, and mortality in the Multiple Risk Factor Intervention Trial.
        Am J Cardiol. 1985; 55: 1-15
        • Multiple Risk Factor Intervention Trial Research Group
        Exercise electrocardiogram and coronary heart disease mortality in the Multiple Risk Factor Intervention Trial.
        Am J Cardiol. 1985; 55: 16-24
        • 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: 99-118