• Dipak Kotecha, Jane Holmes, Henry Krum, Douglas G Altman, Luis Manzano, John G F Cleland, Gregory Y H Lip, Andrew J S Coats, Bert Andersson, Paulus Kirchhof, Thomas G von Lueder, Hans Wedel, Giuseppe Rosano, Marcelo C Shibata, Alan Rigby, Marcus D Flather, and Beta-Blockers in Heart Failure Collaborative Group.
• University of Birmingham Centre for Cardiovascular Sciences, Birmingham, UK; Clinical Trials and Evaluation Unit, Royal Brompton and Harefield NHS Trust, London, UK; Centre of Cardiovascular Research and Education in Therapeutics, Monash University, Melbourne, VIC, Australia. Electronic address: d.kotecha@bham.ac.uk.
• Lancet. 2014 Dec 20; 384 (9961): 223522432235-43.

BackgroundAtrial fibrillation and heart failure often coexist, causing substantial cardiovascular morbidity and mortality. β blockers are indicated in patients with symptomatic heart failure with reduced ejection fraction; however, the efficacy of these drugs in patients with concomitant atrial fibrillation is uncertain. We therefore meta-analysed individual-patient data to assess the efficacy of β blockers in patients with heart failure and sinus rhythm compared with atrial fibrillation.MethodsWe extracted individual-patient data from ten randomised controlled trials of the comparison of β blockers versus placebo in heart failure. The presence of sinus rhythm or atrial fibrillation was ascertained from the baseline electrocardiograph. The primary outcome was all-cause mortality. Analysis was by intention to treat. Outcome data were meta-analysed with an adjusted Cox proportional hazards regression. The study is registered with Clinicaltrials.gov, number NCT0083244, and PROSPERO, number CRD42014010012.Findings18,254 patients were assessed, and of these 13,946 (76%) had sinus rhythm and 3066 (17%) had atrial fibrillation at baseline. Crude death rates over a mean follow-up of 1·5 years (SD 1·1) were 16% (2237 of 13,945) in patients with sinus rhythm and 21% (633 of 3064) in patients with atrial fibrillation. β-blocker therapy led to a significant reduction in all-cause mortality in patients with sinus rhythm (hazard ratio 0·73, 0·67-0·80; p<0·001), but not in patients with atrial fibrillation (0·97, 0·83-1·14; p=0·73), with a significant p value for interaction of baseline rhythm (p=0·002). The lack of efficacy for the primary outcome was noted in all subgroups of atrial fibrillation, including age, sex, left ventricular ejection fraction, New York Heart Association class, heart rate, and baseline medical therapy.InterpretationBased on our findings, β blockers should not be used preferentially over other rate-control medications and not regarded as standard therapy to improve prognosis in patients with concomitant heart failure and atrial fibrillation.FundingMenarini Farmaceutica Internazionale (administrative support grant).Copyright © 2014 Elsevier Ltd. All rights reserved.

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