Revisiting Beta-Blockers in Heart Failure With Preserved Ejection Fraction—A Systematic Review and Meta-analysis

Despite advances in device therapy and the emergence of novel treatments, beta-blockers (BBs) remain a commonly prescribed medication in heart failure (HF). However, HF with preserved ejection fraction (HFpEF) is underdiagnosed and undertreated, and the specific role of BB therapy in this population remains controversial. A comprehensive search was conducted on PubMed, Embase, and Cochrane databases to identify studies evaluating the impact of BB use on clinical outcomes in patients with HFpEF. Data were pooled using a random-effects model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and heterogeneity was assessed using I² statistics. We identified 13 observational studies comprising 442,543 patients, of whom 48.3% were women, with a mean age of 76.0 ± 8.3 years. In pooled analyses, BB use was associated with a lower risk of all-cause mortality (HR 0.81, 95% CI 0.73-0.90, p < 0.001). BB therapy was also associated with lower risks of cardiovascular death (HR 0.76, 95% CI 0.64-0.90, p < 0.01), HF hospitalization (HR 0.88, 95% CI 0.78-1.00, p = 0.05), and the composite outcome of death or HF hospitalization (HR 0.89, 95% CI 0.82-0.98, p = 0.02). In conclusion, in this observational meta-analysis, BB use was associated with lower mortality risk in HFpEF, whereas associations with hospitalization outcomes were heterogeneous. These findings should be interpreted as hypothesis-generating and warrant confirmation in adequately powered randomized trials.