Clinical effects of β-adrenergic blockade in chronic heart failure: A meta-analysis of double-blind, placebo-controlled, randomized trials

Background - β-Blockers have improved symptoms and reduced the risk of 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 trials of β- blockers in heart failure. From this combined database of 3023 patients, we evaluated the strength of evidence supporting an effect of treatment on left ventrical ejection fraction, NYHA functional class, hospitalizations for heart failure, and death. β-Blockers exerted their most persuasive effects on ejection fraction and on the combined risk of death and hospitalization for heart failure. β-Blockade increased the ejection fraction by 29% (P<10^{- 9}) and reduced the 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 β-blockade on NYHA functional class was of borderline significance (P=0.04) and disappeared with the addition or removal of only 1 moderate-size study. Although β-blockade reduced all-cause mortality by 32% (P=0.003), this effect was only moderately robust and varied according to the type of β- blocker tested, ie, the reduction of mortality risk was greater for nonselective β-blockers than for β₁-selective agents (49% versus 18%, P=0.049). However, selective and nonselective β-blockers did not differ in their effects on other measures of clinical efficacy. Conclusions - These analyses indicate that there is persuasive evidence supporting a favorable effect of β-blockade on ejection fraction and the combined risk of death and hospitalization for heart failure. In contrast, the effect of these drugs on other end points requires additional study.