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

Journal article

 To determine the efficacy and tolerability of β 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. Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction <0.45. 13 833 patients from 11 trials; median age 64; 24% women. The 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. Compared with placebo, β 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 β 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 β blockers, 15.6% in those receiving placebo). Irrespective of age or sex, patients with HFrEF in sinus rhythm should receive β blockers to reduce the risk of death and admission to hospital.Registration PROSPERO CRD42014010012; Clinicaltrials.govNCT00832442.

Authors: Kotecha, D; Manzano, L; Krum, H; Rosano, G; Holmes, J

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BMJ Publishing Group
• Journal: BMJ (Clinical research ed.)
• Volume: 353
• Pages: i1855
• Publication date: 2016-04-20
• Acceptance date: 2016-03-14
• DOI: 10.1136/bmj.i1855
• EISSN: 1756-1833
• ISSN: 0959-8138
• Language: English
• Keywords: SBTMR; Beta-Blockers in Heart Failure Collaborative Group