Bm. Psaty et al., HEALTH OUTCOMES ASSOCIATED WITH ANTIHYPERTENSIVE THERAPIES USED AS FIRST-LINE AGENTS - A SYSTEMATIC REVIEW AND METAANALYSIS, JAMA, the journal of the American Medical Association, 277(9), 1997, pp. 739-745
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.