Finlay A. McAlister, MD, MSc; Natasha Wiebe, MMath, PStat; Justin A. Ezekowitz, MD, MSc; Alexander A. Leung, MD; Paul W. Armstrong, MD
Guidelines recommend that patients with heart failure receive Î²-blockers in doses used in the trials that have proven their efficacy. Although the adverse effects of Î²-blockade are dose-related, it is unclear whether the benefits are.
To determine whether the survival benefits of Î²-blockade in heart failure are associated with the magnitude of heart rate reduction or the Î²-blocker dose.
MEDLINE, EMBASE, CINAHL, SIGLE, Web of Science, and the Cochrane Central Register of Controlled Trials, supplemented by hand-searches of bibliographies.
Randomized, placebo-controlled heart failure trials that reported all-cause mortality.
Two reviewers independently extracted data on study characteristics, Î²-blocker dosing and heart rate reduction, and death.
The mean left ventricular ejection fraction in the 23 Î²-blocker trials ranged from 0.17 to 0.36, and more than 95% of the 19Â 209 patients had systolic dysfunction. The overall risk ratio for death was 0.76 (95% CI, 0.68 to 0.84); however, heterogeneity testing revealed moderate heterogeneity among trials (I2Â = 30%), which was associated with the magnitude of heart rate reduction achieved within each trial (P for meta-regressionÂ = 0.006). For every heart rate reduction of 5 beats/min with Î²-blocker treatment, a commensurate 18% reduction (CI, 6% to 29%) in the risk for death occurred. No significant relationship between all-cause mortality and Î²-blocker dosing was observed (risk ratio for death, 0.74 [CI, 0.64 to 0.86]) in high-dose Î²-blocker trials vs. 0.78 [CI, 0.63 to 0.96] in low-dose Î²-blocker trials; P for meta-regressionÂ = 0.69).
The analysis is based on aggregate data and resting heart rates. Few patients in these trials had bradycardia or diastolic dysfunction at baseline.
The magnitude of heart rate reduction is statistically significantly associated with the survival benefit of Î²-blockers in heart failure, whereas the dose of Î²-blocker is not.
McAlister FA, Wiebe N, Ezekowitz JA, et al. Meta-analysis: β-Blocker Dose, Heart Rate Reduction, and Death in Patients With Heart Failure. Ann Intern Med. 2009;150:784–794. doi: 10.7326/0003-4819-150-11-200906020-00006
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Published: Ann Intern Med. 2009;150(11):784-794.
Cardiology, Heart Failure.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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