Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Hydrochlorothiazide and amiloride reduced the risk for stroke, coronary events, and cardiovascular events in hypertensive older adults

ACP J Club. 1992 July-Aug;117:1. doi:10.7326/ACPJC-1992-117-1-001


Source Citation

MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ. 1992 Feb 15;304:405-12.


Abstract

Objective

To determine whether treatment reduces the risk for stroke, coronary heart disease, and death from all causes in hypertensive adults aged 65 to 74 years.

Design

Randomized, single-blind, placebo-controlled trial (mean follow-up of 5.8 y).

Setting

226 general practices in England, Scotland, and Wales.

Patients

4396 patients (mean age, 70 y) with hypertension (defined as a mean systolic blood pressure of 160 to 209 mm Hg and mean diastolic blood pressure < 115 mm Hg during an 8-wk run-in period) were included. Exclusion criteria were secondary hypertension; taking antihypertensive medication; cardiac failure; receiving treatment for angina pectoris; myocardial infarction or stroke within 3 months; impaired renal function; diabetes; asthma; or a serum potassium level of ≤ 3.4 mmol/L or > 5.0 mmol/L. 25% of the patients were lost to follow-up.

Intervention

Patients were assigned to atenolol, 50 mg daily (n = 1102); hydrochlorothiazide, 25 mg or 50 mg daily, plus amiloride, 2.5 mg or 5.0 mg daily (n = 1081); or placebo (n = 2213). Beginning in 1985, all patients assigned to the diuretic regimen received the lower dose. Drug regimens for those on active treatment were modified to achieve individual target blood pressures.

Main outcome measures

Stroke, coronary events, and death from all causes. Analysis was by intention-to-treat.

Main results

Compared with placebo, patients receiving active treatment (diuretic and β-blocker groups) had a 25% reduction in stroke (95% CI 3% to 42%) and a 17% reduction in all cardiovascular events (CI 2% to 29%). When compared with placebo and after adjustment for baseline factors, the diuretic group had a 31% reduction in stroke (CI 3% to 51%); a 44% reduction in coronary events (CI 21% to 60%); and a 35% reduction in all cardiovascular events (CI 17% to 49%). None of these end points was significant in the β-blocker group and the rates of coronary events and all cardiovascular events were higher than in the diuretic group.

Conclusion

Hydrochlorothiazide and amiloride reduced the risk for stroke, coronary events, and all cardiovascular events in older hypertensive adults when compared with atenolol and placebo.

Sources of funding: Medical Research Council; Merck Sharp & Dohme; Imperial Chemical Industries; Bayer.

Address for article reprint: Dr. T.W. Meade, MRC Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, Medical College of St. Bartholomew's Hospital, London EC1M 6BQ, United Kingdom.


Commentary

A decade ago clinicians were debating the usefulness of treating hypertension in elderly persons. Although epidemiologic evidence showed a deleterious effect of hypertension, no clinical trials existed, and it was possible that side effects would outweigh any benefit. This article joins several previous studies in convincingly showing a benefit of treating elevations of systolic and combined systolic and diastolic hypertension, especially with a diuretic combination, in persons over 65 years.

Although this study adds weight to the arguments in favor of active treatment of hypertension in the elderly, perhaps the most intriguing element is the comparison between two classes of antihypertensive drug therapy—thiazide diuretics with a potassium-sparing agent compared with β-blockade. Most previous treatment trials have used diuretics as primary agents. Because β-blockers, calcium antagonists, and angiotensin-converting enzyme inhibitors are all also commonly used, it will be useful for future trials to incorporate randomized comparisons between drugs to help determine the optimal regimen. This study showed decreased efficacy and less tolerance for atenolol compared with the diuretic. The lower antihypertensive efficacy makes it difficult to interpret the lack of significant effect of the β-blocker on this trial's primary end points, but this lack of effect is in line with the results of other trials of β-blockers in the elderly. The β-blocker group also had more dropouts than the diuretic group, both for side effects and for inadequate blood pressure control. I hope that this study will spark future studies to answer questions directly about the relative value of different antihypertensive drugs.

Jay S. Luxenberg, MD
The San Francisco Institute on AgingSan Francisco, California, USA