CLINICAL EFFECTS OF BETA-ADRENERGIC-BLOCKADE IN CHRONIC HEART-FAILURE- A METAANALYSIS OF DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED TRIALS

Background-beta-Blockers have improved symptoms and reduced the risk o f cardiovascular events in studies of patients with heart failure, but it is unclear which end points are most sensitive to the therapeutic effects of these drugs. Methods and Results-We combined the results of all 18 published double-blind, placebo-controlled, parallel-group tri als of beta-blockers in heart failure. From this combined database of 3023 patients, we evaluated the strength of evidence supporting an eff ect of treatment on left ventricular ejection fraction, NYHA functiona l class, hospitalizations for heart failure, and death, beta-Blockers exerted their most persuasive effects on ejection fraction and on the combined risk of death and hospitalization for heart failure. beta-Blo ckade increased the ejection fraction by 29% (P<10(-9)) and reduced th e combined risk of death or hospitalization for heart failure by 37% ( P<0.001). Both effects remained significant even if >90% of the trials were eliminated from the analysis or if a large number of trials with a neutral result were added to the analysis. In contrast, the effect of beta-blockade on NYHA functional class was of borderline significan ce (P=0.04) and disappeared with the addition or removal of only 1 mod erate-size study. Although beta-blockade reduced all-cause mortality b y 32% (P=0.003), this effect was only moderately robust and varied acc ording to the type of beta-blocker tested, ie, the reduction of mortal ity risk was greater for nonselective beta-blockers than for beta(1)-s elective agents (49% versus 18%, P=0.049). However, selective and nons elective beta-blockers did not differ in their effects on other measur es of clinical efficacy. Conclusions-These analyses indicate that ther e is persuasive evidence supporting a favorable effect of beta-blockad e on ejection fraction and the combined risk of death and hospitalizat ion for heart failure. In contrast, the effect of these drugs on other end points requires additional study.