Effect of age and sex on efficacy and tolerability of beta blockers in patients with heart failure with reduced ejection fraction:individual patient data meta-analysis

OBJECTIVESTo determine the efficacy and tolerability of beta blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials.DESIGNProspectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction <0.45.PARTICIPANTS13 833 patients from 11 trials; median age 64; 24% women.MAIN OUTCOME MEASURESThe primary outcome was all cause mortality; the major secondary outcome was admission to hospital for heart failure. Analysis was by intention to treat with an adjusted one stage Cox proportional hazards model.RESULTSCompared with placebo, beta blockers were effective in reducing mortality across all ages: hazard ratios were 0.66 (95% confidence interval 0.53 to 0.83) for the first quarter of age distribution (median age 50); 0.71 (0.58 to 0.87) for the second quarter (median age 60); 0.65 (0.53 to 0.78) for the third quarter (median age 68); and 0.77 (0.64 to 0.92) for the fourth quarter (median age 75). There was no significant interaction when age was modelled continuously (P=0.1), and the absolute reduction in mortality was 4.3% over a median follow-up of 1.3 years (number needed to treat 23). Admission to hospital for heart failure was significantly reduced by beta blockers, although this effect was attenuated at older ages (interaction P=0.05). There was no evidence of an interaction between treatment effect and sex in any age group. Drug discontinuation was similar regardless of treatment allocation, age, or sex (14.4% in those give beta blockers, 15.6% in those receiving placebo).CONCLUSIONIrrespective of age or sex, patients with HFrEF in sinus rhythm should receive beta blockers to reduce the risk of death and admission to hospital.