Systematic review of antihypertensive therapies: Does the evidence assist in choosing a first-line drug?

Background: The available evidence about the effectiveness of specific firs t-line antihypertensive drugs in lowering blood pressure and preventing adv erse 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 contro lled trials of at least 1 year's duration that provided morbidity or mortal ity data and that compared 1 of 6 possible first-line antihypertensive ther apies 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 dru g-no treatment comparison) and the drug therapy: death, stroke, coronary ar tery 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: thiazi des (21 trials), beta-adrenergic blockers (5), calcium-channel blockers (4) and angiotensin-converting-enzyme (ACE) inhibitors (1). in 5 drug-drug tri als 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 [Cl] 0.63-0.76). In the trials that had an untreated control group, low-dose thiazide therapy was associated w ith a significant reduction in the risk of death (RR 0.89, 95% CI 0.81-0.99 ), stroke (RR 0.66, 95% Cl 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 th erapy did not significantly reduce the risk of death or coronary artery dis ease. When the results for total cardiovascular events were expressed in te rms 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 approximat ely 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 red ucing systolic blood pressure than the other drug classes. Interpretation: Low-dose thiazide therapy can be prescribed as the first-li ne treatment of hypertension with confidence that the risk of death, corona ry artery disease and stroke will be reduced. The same cannot be said for h igh-dose thiazide therapy, beta-blockers, calcium-channel blockers or ACE i nhibitors.