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Abstract
Introduction Beta-blockers (BB) have systematically proven to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Their use is recommended by the NICE guidelines for managing HFrEF. Controversially, BB are also commonly prescribed to treat heart failure with preserved ejection fraction (HFpEF) despite contradicting evidence regarding their benefit. Furthermore, recent data has suggested that potential adverse effects might incur from BB treatment in this patient group. This project aimed to investigate the effect of BB on all-cause mortality and cardiovascular mortality as well as all-cause hospitalisations and heart failure (HF) hospitalisations in patients with HFpEF.
Methods A comprehensive meta-analysis of randomised control trials (RCTs) and observational cohort studies (OCSs) published up to October 2023 was performed. The OCSs were further subdivided between those with propensity score (PS) analyses and those without. Study inclusion criteria were (i) a HFpEF diagnosis defined by a left-ventricular ejection fraction of ≥ 40% or ≥ 50% on cardiac magnetic resonance and/or cardiac positron emission tomography and/or trans-thoracic echocardiogram, (ii) the intervention was either the initiation or continuation of BB treatment, (iii) the comparator was no BB treatment or placebo, (iv) at least one of the following outcomes must have been measured : all-cause mortality, cardiovascular mortality, all-cause hospitalisation, HF hospitalisation and a composite of all-cause mortality and/or HF hospitalisation.
Results A total of 19 studies were selected from an electronic databases search : 3 RCTs (1 046 participants), 10 OCSs with PS analysis (455 220 participants) and 6 OCSs without PS analysis (16 247 participants). Overall, BB treatment was associated with a significant 17% reduction of all-cause mortality compared with no BB treatment (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.77–0.89). Significant statistical heterogeneity was observed between OCSs, both with and without PS analysis (I-squared = 86.7% and 56.0% respectively). The meta-analysis yielded insignificant results for cardiovascular mortality, all-cause hospitalisations, HF hospitalisations as well as the composite of all-cause mortality and/or HF hospitalisations (RR 0.85, 95% CI 0.66–1.09 ; RR 0.96, 95% CI 0.90–1.03 ; RR 1.15, 95% CI 0.84–1.56 and RR 0.93, 95% CI 0.81–1.05 respectively).
Conclusion This review suggests a potential benefit of BB treatment in reducing all-cause mortality in patients with HFpEF ; however, their effect on cardiovascular mortality, all-cause hospitalisation and HF hospitalisation remains unclear. Data was predominantly obtained from OCSs. This highlights a lack of rigorous and adequately powered clinical trials within the current pool of evidence.
Forest plot illustrating the pooled study effect of BB treatment vs. no BB treatment or placebo on all-cause mortality
Conflict of Interest None.