The impact of beta-blocker treatment on all-cause mortality and rehospitalization in general population with heart failure with preserved ejection fraction and comorbidity-specific subgroups

Introduction The benefits of beta-blocker treatment in heart failure have been firmly established in individuals with reduced ejection fraction (EF), yet the debate persists regarding the potential effects of this therapy among patients with EF > 40%, with particularly conflicting results in those diagnosed with heart failure with preserved ejection fraction (HFpEF). Purpose This study aimed to evaluate the association and possible comorbidity-specific effects of beta-blocker treatment with all-cause mortality and rehospitalization among individuals diagnosed with HFpEF. Methods The study included HFpEF patients (N=4,397, 52% female, median [Q1, Q3] age 74 [66, 81] years), from the Academic Repository of Clinical Cases of a Medical University (2018–2025). Subjects were grouped according to beta-blocker treatment status, established through a review of electronic health records. The association between therapy and the study’s endpoints (all-cause mortality, rehospitalization), was examined using confounder-adjusted Cox proportional hazards models. The median follow-up time was 35 (14, 64) months. Interaction terms with history of myocardial infarction (MI), arterial hypertension and atrial fibrillation were included one-by-one to screen for comorbidity-specific effects of the therapy. Results Of the analyzed population (Table 1), 2,051 (46.6%) patients had previously received beta-blockers. The effect of beta-blockers on mortality was not significant, with an adjusted hazard ratio (aHR) of 0.96 (95% CI: 0.75–1.23) and deaths percentage was comparable between the groups (8.2% for treated vs. 8.6% for not treated, p = 0.74). Analysis of the comorbidity-specific effects revealed that beta-blocker therapy was associated with increased risk of rehospitalization but only when accompanied by a history of MI (main effect aHR of 1.19, 95% CI: 0.91-1.56, significant interaction term with aHR of 1.86, 95% CI: 1.03-3.34, p=0.039). Rehospitalization rate did not differ significantly between the treatment arms (10.9% of treated vs. 9.2% of untreated, p = 0.07). The proportion of rehospitalization in patients treated with beta-blockers and past MI was 17.2% and was significantly larger than in groups without treatment and/or MI history (Figure 1). There were no significant interactions of beta-blockers use with arterial hypertension and atrial fibrillation in regards to the analyzed end-points. Conclusions Beta-blocker therapy do not reduce mortality in the HFpEF cohort. Moreover, it may be associated with an increased risk of rehospitalization in patients with previous MI. Further studies are necessary to clarify the role of beta-blocker use in this inhomogeneous population.