Effect of Beta-Blockade on Mortality in Patients With Heart Failure: Meta-Analysis of Randomized Clinical Trials

Objectives. We sought to evaluate the current evidence for an effect of beta-blockade treatment on mortality in patients with congestive heart failure (CHF). Background. Although numerous small studies have suggested benefit with beta-blocker therapy in patients with heart failure, clear survival benefit has not been demonstrated. recent combined analysis of several studies with the alpha- and beta-adrenergic blocking agent carvedilol demonstrated significant survival advantage; however, the total number of events was small. Furthermore, it is unclear if previous studies with other beta-blockers are consistent with this finding. Methods. Randomized clinical trials of beta-blockade treatment in patients with CHF from January 1975 through February 1997 were identified using MEDLINE search and review of reports from scientific meetings. Studies were included if mortality was reported during 3 or more months of follow-up. Results. We identified 35 reports, 17 of which met the inclusion criteria. These studies included 3,039 patients with follow-up ranging from 3 months to 2 years. Beta-blockade was associated with trend toward mortality reduction in 13 studies. When all 17 reports were combined, beta-blockade significantly reduced all-cause mortality (random effect odds ratio [OR] 0.69, 95% confidence interval [CI] 0.54 to 0.88). trend toward greater treatment effect was noted for nonsudden cardiac death (OR 0.58, 95% CI 0.40 to 0.83) compared with sudden cardiac death (OR 0.84, 95% CI 0.59 to 1.2). Similar reductions in mortality were observed for patients with ischemic (OR 0.69, 95% CI 0.49 to 0.98) and nonischemic cardiomyopathy (OR 0.69, 95% CI 0.47 to 0.99). The survival benefit was greater for trials of the drug carvedilol (OR 0.54, 95% CI 0.36 to 0.81) than for noncarvedilol drugs (OR 0.82, 95% CI 0.60 to 1.12); however, the difference did not reach statistical significance (p = 0.10). Conclusions. Pooled evidence suggests that beta-blockade reduces all-cause mortality in patients with CHF. Additional trials are required to determine whether carvedilol differs in its effect from other agents.