Beta-Blockers for Heart Failure With Atrial Fibrillation

Study Questions:

What is the impact of beta-blockers on mortality and hospitalizations among patients with both atrial fibrillation (AF) and heart failure with a reduced ejection fraction (HFrEF)?

Methods:

From a total of 1,376 patients randomized in the AF-CHF (Atrial Fibrillation-Congestive Heart Failure) trial, those without beta-blockers at baseline were propensity matched to a maximum of two exposed patients. All absolute standardized differences after matching were ≤10%. Primary analyses respected the intention-to-treat principle. In on-treatment sensitivity analyses, beta-blocker status was modeled as a time-dependent covariate. To assess the association between beta-blockers and outcomes, Kaplan-Meier event-free survival curves were estimated, and Cox proportional hazards analyses were conducted separately for each outcome.

Results:

Baseline characteristics were comparable among the matched cohorts (mean age 70 ± 11 years, 81% male, and mean left ventricular EF 27 ± 6%). During a median follow-up of 37 months, beta-blockers were associated with significantly lower all-cause mortality (hazard ratio [HR], 0.721; 95% confidence interval [CI], 0.549-0.945; p = 0.0180), but not hospitalizations (HR, 0.886; 95% CI, 0.715-1.100; p = 0.2232). Similar results were obtained in sensitivity analyses that modeled beta-blockers as a time-dependent variable (HR, 0.668 for all-cause mortality; 95% CI, 0.511-0.874; p = 0.0032; HR, 0.814 for hospitalizations; 95% CI, 0.653-1.014; p = 0.0658). There were no significant interactions between beta-blockers and patterns (i.e., persistent vs. paroxysmal) or burden of AF with respect to mortality or hospitalizations.

Conclusions:

The authors concluded that beta-blockers were associated with significantly lower mortality, but not hospitalizations in patients with HFrEF and AF, irrespective of the pattern or burden of AF.

Perspective:

This propensity-matched study reports that beta-blockers were associated with a 28% reduction in all-cause mortality in patients with HFrEF and AF. The magnitude of effect was even more pronounced in an on-treatment analysis, with beta-blockers associated with 33% lower mortality. Furthermore, the mortality reduction was not related to AF characteristics, including type of AF (i.e., paroxysmal or persistent), proportion of time spent in AF, and time since first diagnosis. Overall, these data support current guideline recommendations to prescribe beta-blockers in all patients with HFrEF without contraindications, regardless of the presence or absence of coexisting AF. Additional studies are indicated to assess whether the mortality reduction associated with beta-blockers in this patient population is a class effect and if there is a dose–response relationship.

Clinical Topics: Arrhythmias and Clinical EP, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure

Keywords: Adrenergic beta-Antagonists, Arrhythmias, Cardiac, Atrial Fibrillation, Disease-Free Survival, Geriatrics, Heart Failure, Hospital Mortality, Stroke Volume


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