Beta-blockers in heart failure with preserved ejection fraction: a meta-analysis

Beta-blockers are established drugs in heart failure with reduced ejection fraction, but their role in heart failure with preserved ejection fraction (HFpEF) is not established. Hence, we undertook a meta-analysis to evaluate the efficacy of beta-blockers on mortality and morbidity in HFpEF patients. A systematic search using PubMed, Embase, Scopus and Cochrane databases was performed to identify all relevant studies on beta-blockers and HFpEF. A random-effects model was performed to assess the role of beta-blockers on all-cause mortality and HF hospitalization. Overall 15 observational studies and two randomized control trial involving a total of 27,099 patients were included in the analysis. In the observational studies, beta-blocker therapy was associated with lower all-cause mortality [RR 0.81 (0.72-0.90), p < 0.001], but not HF hospitalization [RR 0.79 (0.57-1.10), p < 0.001]. However, in the two RCTs, the use of beta-blocker was not associated with all-cause mortality [RR 0.94 (0.67-1.32), p = 0.72] or HF hospitalization [0.90 (0.54-1.49), p = 0.68]. The results were consistent by geographic region (USA vs. rest of world) and ejection fraction subgroups. Subgroup analysis revealed that the beneficial survival effect of beta-blocker was limited to studies with mean age < 75 years. Observational studies showed a significant benefit from the use of beta-blockers for all-cause mortality, but not for HF hospitalization. Beta-blockers in the two RCTs were not associated with significant reduction in all-cause mortality or HF hospitalization; however, both the trials were not adequately powered and had high loss to follow-up rates. Further large sampled well-conducted randomized trials are warranted to confirm the effects of beta-blockers on mortality and hospitalization.