Meta-analysis: β-Blocker Dose, Heart Rate Reduction, and Death in Patients With Heart Failure

    loading  Checking for direct PDF access through Ovid



Guidelines recommend that patients with heart failure receive β-blockers in doses used in the trials that have proven their efficacy. Although the adverse effects of β-blockade are dose-related, it is unclear whether the benefits are.


To determine whether the survival benefits of β-blockade in heart failure are associated with the magnitude of heart rate reduction or the β-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, β-blocker dosing and heart rate reduction, and death.

Data Synthesis:

The mean left ventricular ejection fraction in the 23 β-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 β-blocker treatment, a commensurate 18% reduction (CI, 6% to 29%) in the risk for death occurred. No significant relationship between all-cause mortality and β-blocker dosing was observed (risk ratio for death, 0.74 [CI, 0.64 to 0.86]) in high-dose β-blocker trials vs. 0.78 [CI, 0.63 to 0.96] in low-dose β-blocker trials; P for meta-regression = 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 β-blockers in heart failure, whereas the dose of β-blocker is not.

Related Topics

    loading  Loading Related Articles