HEALTH OUTCOMES ASSOCIATED WITH ANTIHYPERTENSIVE THERAPIES USED AS FIRST-LINE AGENTS - A SYSTEMATIC REVIEW AND METAANALYSIS

Objective.-To review the scientific evidence concerning the safety and efficacy of various antihypertensive therapies used as first-line age nts and evaluated in terms of major disease end points. Data Sources.- MEDLINE searches and previous meta-analyses for 1980 to 1995. Data Sel ection.-We selected long-term studies that assessed major disease end points as an outcome. For the meta-analysis, we chose placebo-controll ed randomized trials. For randomized trials using surrogate end points such as blood pressure, we selected the largest studies that evaluate d multiple drugs. Where clinical trial evidence was lacking, we relied on information from observational studies. Data Synthesis.-Diuretics and beta-blockers have been evaluated in 18 long-term randomized trial s. Compared with placebo, beta-blocker therapy was effective in preven ting 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, 0.1 7; 95% CI, 0.07-0.41). Low-dose diuretic therapy prevented not only st roke (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) inhib itors reduce blood pressure in hypertensive patients, the clinical tri al evidence in terms of health outcomes is meager. For several short-a cting dihydropyridine calcium channel blockers, the available evidence suggests the possibility of harm. Whether the long-acting formulation s and the nondihydropyridine calcium channel blockers are safe and pre vent 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 b lockers and ACE inhibitors on cardiovascular disease incidence are com pleted, the available scientific evidence provides strong support for the current national guidelines, which recommend diuretics and beta-bl ockers as first-line agents and low-dose therapy for all antihypertens ive agents.