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 Y H, Van Veldhuisen, Dirk J, Shibata, Marcelo C, Wedel, Hans, Böhm, Michael and Flather, Marcus 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, 2016. ISSN 1759-2151

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Abstract

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.

Item Type:	Article
Additional Information:	This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Cardiovascular and Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Norwich Clinical Trials Unit Faculty of Medicine and Health Sciences > Research Groups > Public Health and Health Services Research (former - to 2023)
Depositing User:	Pure Connector
Date Deposited:	03 May 2016 16:00
Last Modified:	04 Nov 2023 02:59
URI:	https://ueaeprints.uea.ac.uk/id/eprint/58547
DOI:	10.1136/bmj.i1855

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