The effect of beta-blockers on mortality in heart failure with preserved ejection fraction: A meta-analysis of observational cohort and randomized controlled studies

Background: Nearly half of patients with heart failure (HF) have preserved ejection fraction (EF) and the mortality of patients with HF with preserved EF (HFpEF) is high. However, there is no therapy to improve survival in HFpEF. Although observational cohort studies (OCSs) have examined the survival benefit of beta-blockers in HFpEF, the results are inconsistent due to limited power with small sample sizes and/or lack of adjustment for known confounders. Furthermore, recent randomized controlled trial (RCT)s failed to show the mortality benefit of beta-blockers in HFpEF. However, these RCTs were not adequately powered and thus the definite conclusion cannot be drawn. Methods and results: We aimed to conduct a meta-analysis of the effect of beta-blockers on mortality in HFpEF. The search of electronic databases identified 5 OCSs with propensity score (PS) analysis (12,315 patients), 6 OCSs without PS analysis (15,275 patients), and 3 RCTs (1046 patients). Beta-blocker use was associated with improved survival in the pooled analysis of OCSs with PS analysis (RR [95% CI] = 0.79 [0.66-0.95]) and in that of OCSs without PS analysis (0.70 [0.52-0.94]). In the pooled analysis of RCTs, beta-blocker use was associated with non-significant reduced risk for mortality (RR [95% CI]= 0.80 [0.61-1.05]). Overall, use of beta-blockers reduced the risk of mortality by 21% (RR [95% CI] = 0.79 [0.71-0.88]). Conclusion: Our meta-analysis suggests the potential mortality benefit of beta-blockers in HFpEF. Well-designed and powered RCTs should be planned to confirm our observed potential survival benefit of beta-blockers in HFpEF. (C) 2016 Elsevier Ireland Ltd. All rights reserved.