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

Kotecha, D. et al. (2016) 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. British Medical Journal, 353, i1855. (doi: 10.1136/bmj.i1855) (PMID:27098105) (PMCID:PMC4849174)

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Objectives: 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. Design: 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. Participants: 13 833 patients from 11 trials; median age 64; 24% women. Main outcome measures: 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. Results: 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). Conclusion 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.gov NCT00832442.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Cleland, Professor John
Authors: Kotecha, D., Manzano, L., Krum, H., Rosano, G., Holmes, J., Altman, D. G., Collins, P. D., Packer, M., Wikstrand, J., Coats, A. J.S., Cleland, J. G.F., Kirchhof, P., von Lueder, T. G., Rigby, A. S., Andersson, B., Lip, G. Y.H., van Veldhuisen, D. J., Shibata, M. C., Wedel, H., Böhm, M., and Flather, M. D.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:British Medical Journal
Publisher:BMJ Publishing Group
ISSN (Online):1756-1833
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in BMJ 353: i1855
Publisher Policy:Reproduced under a Creative Commons License

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