Background: Beta-blockers are recommended in heart failure patients with reduced ejection fraction (HFrEF) and sinus rhythm, but prescription rates are consistently lower in older patients and women.
Objectives: We sought to determine the efficacy and tolerability of beta-blockers in a broad age-range of adult women and men with HFrEF by pooling individual patient data (IPD) from placebo-controlled randomized trials.
Methods: The study was a prospectively designed IPD meta-analysis of patients aged 40-85 years in sinus rhythm at baseline, with left-ventricular ejection fraction <0.45. The primary outcome was all-cause mortality and major secondary outcome heart failure hospitalization. Analysis was by intention to treat using an adjusted one-stage Cox proportional hazards model. Registration: PROSPERO CRD42014010012; Clinicaltrials.gov NCT00832442.
Results: 13,833 patients were included from 11 trials, with median age 64 years and 24% women. Beta-blockers were effective in reducing mortality versus placebo across all ages: Quartile 1 (median age 50) hazard ratio (HR) 0.66 (95% CI 0.53 to 0.83); Quartile 2 (median 60) HR 0.71 (0.58 to 0.87); Quartile 3 (median 68) HR 0.65 (0.53 to 0.78); Quartile 4 (median 75) HR 0.77 (0.64 to 0.92). There was no significant interaction when age was modelled continuously (p=0.10) and the absolute mortality reduction was 4.3% over a median follow-up of 1.3 years (number needed to treat=23). Heart failure hospitalization was significantly reduced by beta-blockers, although this effect was attenuated at older age (interaction p=0.05). There was no evidence of an interaction between treatment effect and gender in any age group. Drug discontinuation was similar regardless of treatment allocation, age or gender (14.4% beta-blockers, 15.6% placebo).
Conclusion: Irrespective of age or gender, patients with HFrEF in sinus rhythm should receive beta-blockers to reduce the risk of death and hospitalization.