It has been shown that the use of beta-adrenergic blockers prevents the adverse effects of sympathetic stimulation on the failing heart. Beta blockade has produced favorable results in a large number of randomized, controlled trials. Although two meta-analyses of the effect of beta blockers in heart failure have been published, the emphasis was on rates of mortality, and data from some nonrandomized or uncontrolled trials were included. Lechat and associates combined the results of 18 published double-blind, placebo-controlled and parallel-group trials to include measures not reported in the original publications.
The 18 trials enrolled a total of 3,023 patients with heart failure that was caused by idiopathic dilated cardiopathy and ischemic heart disease. For all end points, there was a significant effect in favor of treatment with beta blockers. Patients taking beta blockers experienced a 32 percent reduction in the risk of death and a 41 percent reduction in hospitalizations compared with the placebo-treated patients. Patients receiving beta blockers also showed a 32 percent improvement in NYHA classification and were 30 percent less likely to have worsening symptoms. The ejection fraction increased by 29 percent in patients treated with beta blockers compared with placebo-treated patients.
Assuming a treatment period identical to the mean duration of follow-up (seven months), the authors determined that physicians would need to treat 38 patients to avoid one death, 24 patients to avoid one hospitalization and 15 patients to avoid one combined end point.
The effects of treatment in trials of nonselective beta blockers were compared with those in trials of beta1-selective agents. The risk of death was reduced by 49 percent in trials of nonselective beta blockers but by only 18 percent in trials of beta1-selective agents. This difference was statistically significant.
The meta-analysis indicates that the use of beta blockers is associated with a reduction in mortality of about 30 percent in patients with heart failure. Any uncertainty about the effect of beta blockers on rates of survival is heightened by the finding that the magnitude of the mortality reduction depends on the pharmacologic properties of the drug used. While selective and nonselective beta blockers increased ejection fractions and decreased hospitalizations in a similar way, nonselective beta blockers were associated with a larger survival benefit than beta1-selective agents. This observation is especially noteworthy because data from postinfarction trials have suggested that agents that block both beta1 and beta2 receptors may provide more complete protection against catecholamine toxicity than agents that act only on the beta1 receptor.
It should be noted that nearly 90 percent of the experience with nonselective beta blockers is with carvedilol, which is known to block alpha-adrenergic receptors in addition to beta1 and beta2 receptors. It is possible that blockage of alpha receptors might account for the larger reduction in mortality observed with nonselective agents in the present analysis.
The authors conclude that unlike other meta-analyses, this analysis did not confine itself to mortality but rather analyzed nonfatal measures of outcome such as hospitalizations. For these variables, the number of events was large and the treatment effects were robust. This meta-analysis demonstrates that the addition of a beta blocker to conventional therapy is associated with hemodynamic and symptomatic improvement as well as favorable effects on morbidity and mortality. Physicians have sufficient evidence to support the use of beta blockers in heart failure.