title: Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis.
abstract: BACKGROUND
  Atrial 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  18,254 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.
  
  
  CONCLUSIONS
  Based 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.
  
  
  BACKGROUND
  Menarini Farmaceutica Internazionale (administrative support grant).
authors.affiliation: 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.
authors.forename: Dipak
authors.initials: D
authors.lastname: Kotecha
authors.affiliation: Centre for Statistics in Medicine, University of Oxford, Oxford, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Holmes
authors.affiliation: Centre of Cardiovascular Research and Education in Therapeutics, Monash University, Melbourne, VIC, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.affiliation: Centre for Statistics in Medicine, University of Oxford, Oxford, UK.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Altman
authors.affiliation: Internal Medicine Department, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Manzano
authors.affiliation: National Heart and Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College, London, UK; Hull York Medical School, University of Hull, Kingston upon Hull, UK.
authors.forename: John G F
authors.initials: JG
authors.lastname: Cleland
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, Birmingham, UK; City Hospital, Sandwell and West Birmingham NHS Trust, Birmingham, UK.
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.affiliation: Monash University, Melbourne, VIC, Australia; Warwick University, Warwick, UK.
authors.forename: Andrew J S
authors.initials: AJ
authors.lastname: Coats
authors.affiliation: Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Bert
authors.initials: B
authors.lastname: Andersson
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, Birmingham, UK; City Hospital, Sandwell and West Birmingham NHS Trust, Birmingham, UK; Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany.
authors.forename: Paulus
authors.initials: P
authors.lastname: Kirchhof
authors.affiliation: Centre of Cardiovascular Research and Education in Therapeutics, Monash University, Melbourne, VIC, Australia; Department of Cardiology, Oslo University Hospital, Oslo, Norway.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: von Lueder
authors.affiliation: Nordic School of Public Health, Gothenburg, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Wedel
authors.affiliation: Department of Medical Sciences, Instituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rosano
authors.affiliation: Division of Cardiology, University of Alberta, Edmonton, Canada.
authors.forename: Marcelo C
authors.initials: MC
authors.lastname: Shibata
authors.affiliation: Academic Cardiology, Castle Hill Hospital, Kingston upon Hull, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Rigby
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, UK.
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Flather
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy* / Q000401:mortality*; D004562:Electrocardiography; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D007902:Length of Stay / Q000706:statistics & numerical data; D010343:Patient Admission / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000401:mortality
chemical_list: D000319:Adrenergic beta-Antagonists