Beta-blockers and heart failure: meta-analysis of mortality trials.
BACKGROUND
Four large double-blind placebo-controlled studies have been performed to address mortality as a primary endpoint in patients with heart failure treated with beta-blockers. Unfortunately, 2 of the studies were stopped in the interim stage, and so these trials may be somewhat underpowered for the estimation of the secondary endpoint, type of death. This endpoint is important, because if patients die for reasons other than progression of heart failure, e.g. arrhythmias, then alternative antiarrhythmic agents may serve equally well or better than beta-blockers and with fewer side effects.


OBJECTIVE
We assessed hazard ratios of all-cause-deaths, sudden deaths, death due to progressive heart failure and serious adverse effects leading to discontinuation of double-blind treatment. Hazard ratio = risk of death in treatment group/risk of death in placebo group.


RESULTS
The pooled results showed a significant reduction in all-cause-deaths of 35% (p < 0.0001). The risk reduction of sudden death, reflecting the occurrence of fatal arrhythmias, similarly, showed a significant risk reduction of 37% (p < 0.0001). However, the risk reduction of death due to progression to heart failure was small (13%) and statistically non-significant, indicating that progression of heart failure, as estimated by numbers of deaths, was not beneficially influenced by the beta-blocker therapy. Finally, the risk of serious adverse effects leading to discontinuation of treatment with beta-blockers, was not significantly different from that for placebo.


CONCLUSIONS
Beta-blockers do not reduce the risk of death due to progression of heart failure. The beneficial effect of beta-blockers is mainly due to a reduced risk of fatal arrhythmias. The risk of serious adverse effects of beta-blockers is not different from that of placebo and so there is little argument to withhold this treatment, even if it does not influence the progression of heart failure.
Cleophas
T J
TJ
European College of Pharmaceutical Medicine, Lyon, France. ajm.cleophas@wxs.nl
Zwinderman
A H
AH
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D004311:Double-Blind Method; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016019:Survival Analysis
D000319:Adrenergic beta-Antagonists