Finlay A. McAlister, MD, MSc; Natasha Wiebe, MMath, PStat; Justin A. Ezekowitz, MD, MSc; Alexander A. Leung, MD; Paul W. Armstrong, MD
Acknowledgment: The authors thank Jeff Bakal, PhD, PStat, for advice on the statistical analyses.
Grant Support: No external funding was received for the study. Dr. McAlister is supported by an Alberta Heritage Foundation for Medical Research Health Scholar Award and holds the Merck Frosst/Aventis Patient Health Management Chair at the University of Alberta. Dr. Ezekowitz is supported by the Canadian Institutes of Health Research.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Finlay A. McAlister, MD, MSc, University of Alberta Hospital, 2F1.21 Walter Mackenzie Health Sciences Centre, 8440 112 Street, Edmonton, Alberta T6G 2R7, Canada; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. McAlister: University of Alberta Hospital, 2F1.21 Walter Mackenzie Health Sciences Centre, 8440 112 Street, Edmonton, Alberta T6G 2R7, Canada.
Dr. Wiebe: University of Alberta, Research Transition Facility, Room 3048, 8308 114 Street, Edmonton, Alberta T6E 6L7 Canada.
Dr. Ezekowitz: Walter Mackenzie Health Sciences Centre, 2C2 Cardiology, 8440 112 Street, Edmonton, Alberta T6G 2B7, Canada.
Dr. Leung: 2F1 Walter Mackenzie Health Sciences Centre, University of Alberta Hospital, 8440 112 Street, Edmonton, Alberta T6G 2R7, Canada.
Dr. Armstrong: University of Alberta, VIGOUR Centre, 251 Medical Sciences Building, Edmonton, Alberta T6G 2H7, Canada.
Author Contributions: Conception and design: F.A. McAlister, N. Wiebe.
Analysis and interpretation of the data: F.A. McAlister, N. Wiebe, J.A. Ezekowitz, P.W. Armstrong.
Drafting of the article: F.A. McAlister, P.W. Armstrong.
Critical revision of the article for important intellectual content: F.A. McAlister, N. Wiebe, J.A. Ezekowitz, A.A. Leung, P.W. Armstrong.
Final approval of the article: F.A. McAlister, N. Wiebe, J.A. Ezekowitz, A.A. Leung, P.W. Armstrong.
Provision of study materials or patients: F.A. McAlister, J.A. Ezekowitz.
Statistical expertise: N. Wiebe.
Administrative, technical, or logistic support: F.A. McAlister.
Collection and assembly of data: F.A. McAlister, J.A. Ezekowitz, A.A. Leung.
McAlister FA, Wiebe N, Ezekowitz JA, Leung AA, Armstrong PW. 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.
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.
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Cardiology, Heart Failure.
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