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, Dipak; Manzano, Luis; Krum, Henry; Rosano, Giuseppe; Holmes, Jane; Altman, Douglas G; Collins, Peter D; Packer, Milton; Wikstrand, John; Coats, Andrew J S; Cleland, John G F; Kirchhof, Paulus; von Lueder, Thomas G; Rigby, Alan S; Andersson, Bert; Lip, Gregory YH; van Veldhuisen, Dirk J; Shibata, Marcelo C; Wedel, Hans; Böhm, Michael; Flather, Marcus D

Abstract

© BMJ Publishing Group Ltd 2016. 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.

Citation

Kotecha, D., Manzano, L., Krum, H., Rosano, G., Holmes, J., Altman, D. G., …Flather, M. D. (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. BMJ, 353, i1855. https://doi.org/10.1136/bmj.i1855

• Journal Article Type: Article
• Acceptance Date: Mar 14, 2016
• Online Publication Date: Apr 20, 2016
• Publication Date: Apr 20, 2016
• Deposit Date: Mar 3, 2018
• Journal: BMJ (Online)
• Print ISSN: 0959-8138
• Electronic ISSN: 1756-1833
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 353
• Pages: i1855
• DOI: https://doi.org/10.1136/bmj.i1855
• Public URL: https://hull-repository.worktribe.com/output/706823
• Publisher URL: http://www.bmj.com/content/353/bmj.i1855