The effect of beta-blockers in heart failure with preserved ejection fraction and atrial fibrillation: systematic review and meta-analysis.

Abstract

Background: Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) frequently coexist and together confer a substantially elevated risk of adverse cardiovascular outcomes. Despite the widespread clinical use of beta-blockers for rate control in this population, their prognostic impact remains unresolved, with existing evidence derived predominantly from observational cohorts subject to confounding by indication.

Aims: To evaluate the association of beta-blocker therapy with all-cause mortality, cardiovascular mortality, heart failure hospitalization, and composite outcomes in patients with coexisting HFpEF and AF through a systematic review and meta-analysis.

Methods: Online databases (MEDLINE and Scopus) were searched from inception through March 2026 for studies reporting on the effects of beta-blockers in patients with HFpEF and AF. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using the DerSimonian and Laird random-effects model. Heterogeneity was quantified using the I² statistic. Leave-one-out sensitivity analyses and pre-specified subgroup analyses by study design and follow-up duration were performed.

Results: Nine studies were included (n = 31,888; beta-blocker group n = 24,683; control n = 7,205). Beta-blocker therapy was associated with a statistically significant reduction in all-cause mortality (HR: 0.88; 95% CI: 0.83-0.93; P < 0.0001; I² = 44.9%) and cardiovascular mortality (HR: 0.91; 95% CI: 0.84-0.99; P = 0.023; I² = 0%). No statistically significant differences were observed for heart failure hospitalization (HR: 0.88; 95% CI: 0.70-1.10; P = 0.264; I² = 62.5%) or the composite outcome (HR: 0.89; 95% CI: 0.77-1.02; P = 0.084; I² = 70.7%). In leave-one-out analyses, exclusion of Yang 2020 yielded statistically significant reductions in both all-cause mortality and heart failure hospitalization with elimination or reduction of heterogeneity.

Conclusions: In patients with HFpEF and concomitant AF, beta-blocker therapy is associated with significant reductions in all-cause and cardiovascular mortality. No significant benefit was observed for heart failure hospitalization or composite outcomes in primary analyses, though sensitivity analyses were supportive. These findings, derived from observational data, support a permissive clinical approach to beta-blocker use in this population, particularly for rate control in those with elevated heart rates. Adequately powered randomized controlled trials specifically targeting HFpEF with AF are urgently needed to establish causal efficacy.