Beta-Blocker Use and Heart Failure Outcomes in Mildly Reduced and Preserved Ejection Fraction

Although studies consistently show that beta-blockers reduce morbidity and mortality in patients with reduced ejection fraction (EF), data are inconsistent in patients with heart failure with mildly reduced ejection fraction (HFmrEF) and suggest potential negative effects in heart failure with preserved ejection fraction (HFpEF). The purpose of this study was to examine the association of beta-blockers with heart failure (HF) hospitalization and death in patients with HF and EF ≥40% Beta-blocker use was assessed at first encounter in outpatients ≥65 years of age with HFmrEF and HFpEF in the U.S. PINNACLE Registry (2013-2017). The associations of beta-blockers with HF hospitalization, death, and the composite of HF hospitalization/death were assessed using propensity-score adjusted multivariable Cox regression models, including interactions of EF × beta-blocker use. Among 435,897 patients with HF and EF ≥40% (HFmrEF, n = 75,674; HFpEF = 360,223), 289,377 (66.4%) were using a beta-blocker at first encounter; more commonly in patients with HFmrEF vs HFpEF (77.7% vs 64.0%; P < 0.001). There were significant interactions between EF × beta-blocker use for HF hospitalization, death, and composite of HF hospitalization/death (P < 0.001 for all), with higher risk with beta-blocker use as EF increased. Beta-blockers were associated with decreased risk of HF hospitalization and death in patients with HFmrEF but a lack of survival benefit and a higher risk of HF hospitalization in patients with HFpEF, particularly when EF was >60%. In a large, real-world, propensity score-adjusted cohort of older outpatients with HF and EF ≥40%, beta-blocker use was associated with a higher risk of HF hospitalization as EF increased, with potential benefit in patients with HFmrEF and potential risk in patients with higher EF (particularly >60%). Further studies are needed to understand the appropriateness of beta-blocker use in patients with HFpEF in the absence of compelling indications.