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Systematic review of antihypertensive therapies

Does the evidence assist in choosing a first-line drug?

Dr. Wright is an Associate Professor in the Departments of Pharmacology and Therapeutics and of Medicine, Mr. Lee is enrolled in the MD-PhD program, and Dr. Chambers is an Assistant Clinical Professor in the Department of Health Care and Epidemiology, University of British Columbia, Vancouver, BC.

Abstract

Background: The available evidence about the effectiveness of specific first-line antihypertensive drugs in lowering blood pressure and preventing adverse outcomes has not been systematically quantified in a manner that would assist clinicians in choosing a first-line drug.

Methods: The following literature sources were searched: MEDLINE (1966-1997), the Cochrane Library (1998 CD-ROM, issue 2) and references from previous meta-analyses published from 1980 to 1997. Selected were randomized controlled trials of at least 1 year's duration that provided morbidity or mortality data and that compared 1 of 6 possible first-line antihypertensive therapies either with another 1 of the 6 drug therapies (drug-drug comparison) or with no treatment, including placebo (drug-no treatment comparison). The following outcomes were pooled according to trial design (drug-drug or drug-no treatment comparison) and the drug therapy: death, stroke, coronary artery disease, total cardiovascular events, withdrawal due to adverse effect, and decrease in systolic and diastolic blood pressure.

Results: Of 38 trials identified, 23 (representing 50 853 patients) met the inclusion criteria. Four drug classes were evaluated in the trials: thiazides (21 trials), beta-adrenergic blockers (5), calcium-channel blockers (4) and angiotensin-converting-enzyme (ACE) inhibitors (1). In 5 drug-drug trials comparing thiazides with beta-blockers, the former were associated with a significantly lower rate of withdrawal due to adverse effects (relative risk [RR] 0.69, 95% confidence interval [CI] 0.63-0.76). In the trials that had an untreated control group, low-dose thiazide therapy was associated with a significant reduction in the risk of death (RR 0.89, 95% CI 0.81-0.99), stroke (RR 0.66, 95% CI 0.56-0.79), coronary artery disease (RR 0.71, 95% CI 0.60-0.84) and cardiovascular events (RR 0.68, 95% CI 0.62-0.75). High-dose thiazide therapy, beta-blocker therapy and calcium-channel blocker therapy did not significantly reduce the risk of death or coronary artery disease. When the results for total cardiovascular events were expressed in terms of absolute risk reduction, low-dose thiazide therapy reduced the risk by 5.7% (95% CI 4.2%-7.2%); the number needed to treat (NNT) for approximately 5 years to prevent one event was 18. In both the drug-drug and the drug-no treatment comparison trials, thiazides were significantly better at reducing systolic blood pressure than the other drug classes.

Interpretation: Low-dose thiazide therapy can be prescribed as the first-line treatment of hypertension with confidence that the risk of death, coronary artery disease and stroke will be reduced. The same cannot be said for high-dose thiazide therapy, beta-blockers, calcium-channel blockers or ACE inhibitors.

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