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Background: Guidelines recommend that patients with heart failure
receive -blockers in doses used in the trials that have proven their
efficacy. Although the adverse effects of -blockade are doserelated,
it is unclear whether the benefits are.
Purpose: To determine whether the survival benefits of -blockade
in heart failure are associated with the magnitude of heart rate
reduction or the -blocker dose.
Data Sources: MEDLINE, EMBASE, CINAHL, SIGLE, Web of Science,
and the Cochrane Central Register of Controlled Trials, supplemented
by hand-searches of bibliographies.
Study Selection: Randomized, placebo-controlled heart failure trials
that reported all-cause mortality.
Data Extraction: Two reviewers independently extracted data on
study characteristics, -blocker dosing and heart rate reduction, and
death.
Data Synthesis: The mean left ventricular ejection fraction in the
23 -blocker trials ranged from 0.17 to 0.36, and more than 95%
of the 19 209 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
( I2 30%), which was associated with the magnitude of heart rate
reduction achieved within each trial ( P for meta-regression
0.006). For every heart rate reduction of 5 beats/min with
-blocker treatment, a commensurate 18% reduction (CI, 6% to
29%) in the risk for death occurred. No significant relationship
between all-cause mortality and -blocker dosing was observed
(risk ratio for death, 0.74 [CI, 0.64 to 0.86]) in high-dose -blocker
trials vs. 0.78 [CI, 0.63 to 0.96] in low-dose -blocker trials; P for
meta-regression 0.69).
Limitations: The analysis is based on aggregate data and resting
heart rates. Few patients in these trials had bradycardia or diastolic
dysfunction at baseline.
Conclusion: The magnitude of heart rate reduction is statistically
significantly associated with the survival benefit of -blockers in
heart failure, whereas the dose of -blocker is not.
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