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

Dipak Kotecha, Luis Manzano, Henry Krum, Giuseppe Rosano, Jane Holmes, Douglas G Altman, Peter D. Collins, Milton Packer, John Wikstrand, Andrew J.S. Coats, John George Franklin Cleland, Paulus Kirchhof, Thomas G. Von Lueder, Alan S. Rigby, Bert Andersson, Gregory Y H Lip, Dirk Jan van Veldhuisen, Marcelo C. Shibata, Hans Wedel, Michael BöhmMarcus D. Flather

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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.

Original languageEnglish
Article numberi1855
Pages (from-to)1-9
Number of pages10
JournalThe BMJ
Publication statusPublished - 20 Apr 2016

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