Beta-blockers may reduce mortality in patients with heart failure and reduced ejection fraction (HFrEF) in sinus rhythm, regardless of pre-treatment heart rate, but there is no effect on mortality in patients with atrial fibrillation (AFib), according to research presented April 30 at Heart Failure 2017 in Paris, and simultaneously published in the Journal of the American College of Cardiology.

Dipak Kotecha, PhD, and colleagues examined 14,313 patients in sinus rhythm and 3,065 patients in AFib. Results showed that higher baseline heart rate was associated with greater all-cause mortality in patients with sinus rhythm, but not in patients with AFib. Beta-blockers reduced heart rate by 11 to 12 beats per minute in both sinus rhythm and AFib. The overall hazard ratio (HR) for mortality comparing beta-blockers with placebo for patients in sinus rhythm was 0.73 (95 percent CI 0.67-0.79; p<0.0001) with similar benefit for all three strata of baseline heart rate. However, beta-blockers did not reduce mortality for patients in AFib, either overall (HR 0.96, 95 percent CI 0.81-1.12; p=0.58) or for any baseline heart rate stratum.

The authors also found that at an interim visit, the heart rate achieved by patients in sinus rhythm was more strongly associated with mortality than the change in heart rate from baseline. The lowest mortality in sinus rhythm was observed in patients who attained lower heart rates after beta-blocker therapy. Neither attained nor change in heart rate were associated with survival in patients with AFib.

The authors were unable to determine whether clinicians should strive to achieve a target heart rate or a target does of beta-blocker.

"Ultimately, heart rate and prescribed beta-blocker dose are intimately related; one is a surrogate for the other although the relationship may be complicated by other factors such as genetic variations in beta-blocker response and drug metabolism," the authors write. "Our observation of dose-related differences in mortality in patients assigned to placebo clearly demonstrates that it is unsafe to make strong inference from any analysis of a post-randomization variable such as dose. Dose achieved is itself an outcome, affected by confounding patient factors, adherence, physician preferences and bias, including the perceived risk of adverse outcomes," they conclude.

Keywords: Adrenergic beta-Antagonists, Atrial Fibrillation, Bradycardia, Cardiology, Genetic Variation, Heart Failure, Heart Rate, Random Allocation

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