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Effect of beta-blockade on mortality in patients with heart failure: a meta-analysis of randomized clinical trials
P A Heidenreich1, T T Lee, B M Massie
1Department of Health Research and Policy, Stanford University, California, USA. pah@smi.stanford.edu
Insights
Beta-blockade treatment significantly reduces all-cause mortality in patients with congestive heart failure (CHF). Pooled evidence indicates a survival benefit, though further trials are needed to compare specific beta-blocker agents like carvedilol.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Previous small studies suggested beta-blocker benefits in heart failure, but a clear survival advantage was not established.
- A combined analysis of carvedilol showed a survival advantage, but with a small number of events.
- Consistency of findings across different beta-blockers remained unclear.
Purpose of the Study:
- To evaluate existing evidence on the effect of beta-blockade treatment on mortality in congestive heart failure (CHF) patients.
- To synthesize findings from randomized clinical trials on beta-blocker therapy in CHF.
- To assess the overall impact of beta-blockade on survival in CHF.
Main Methods:
- Systematic review and meta-analysis of randomized clinical trials.
- MEDLINE search and scientific meeting reports from January 1975 to February 1997.
- Inclusion criteria: CHF patients, beta-blockade treatment, and mortality data over ≥3 months follow-up.
Main Results:
- 17 trials involving 3,039 patients met inclusion criteria.
- Beta-blockade significantly reduced all-cause mortality (OR 0.69, 95% CI 0.49 to 0.98).
- Trends suggested greater reduction in nonsudden cardiac death and similar benefits for ischemic and nonischemic cardiomyopathy.
Conclusions:
- Pooled evidence indicates beta-blockade therapy effectively reduces all-cause mortality in patients with congestive heart failure.
- Further research is necessary to ascertain if carvedilol offers a distinct survival benefit compared to other beta-blockers.
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 a benefit with beta-blocker therapy in patients with heart failure, a clear survival benefit has not been demonstrated. A recent combined analysis of several studies with the alpha- and beta-adrenergic blocking agent carvedilol demonstrated a 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 a MEDLINE search and a 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 a 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). A 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.