title: Bradycardia and atrial fibrillation in patients with stable coronary artery disease treated with ivabradine: an analysis from the SIGNIFY study.
abstract: OBJECTIVE
  The aim of this study was to determine the impact of emergent bradycardia and atrial fibrillation (AF) on cardiovascular outcomes in 19 083 patients with stable coronary artery disease (CAD) receiving ivabradine or placebo (SIGNIFY, Study assessInG the morbidity-mortality beNefits of the If inhibitor ivabradine in patients with coronarY artery disease).
  
  
  RESULTS
  Emergent bradycardia (resting heart rate <50 b.p.m. on 12-lead electrocardiogram) with ivabradine was reported in 3572 patients (37.4%) overall, and in 2242 (37.2%) patients with Canadian Cardiovascular Society (CCS) class ≥ 2 angina. There was no difference in outcomes over the course of the study in ivabradine-treated patients with and without emergent bradycardia in the whole population (2.5 vs. 2.9% per year, respectively, for primary composite endpoint of cardiovascular death or non-fatal myocardial infarction) or in the angina subgroup (2.5 vs. 3.2% per year). Neither was there an increase in the rate of primary endpoint after emergent bradycardia was recorded compared with those without emergent bradycardia. There were 754 cases of emergent AF on treatment (2.2% per year ivabradine vs. 1.5% per year placebo) and 469 in the patients with angina (2.2 vs. 1.5% per year). While outcomes occurred more frequently in patients in whom emergent AF had been recorded, there was no treatment-placebo difference in outcomes, including stroke, and no difference in treatment effect in patients with limiting angina.
  
  
  CONCLUSIONS
  Both in the overall population as well as in the angina subset, bradycardia was common in ivabradine-treated patients, but did not appear to impact outcomes. Emergent AF was relatively rare and did not appear to have an impact on outcomes relative to placebo.
  
  
  BACKGROUND
  ISRCTN61576291.
authors.affiliation: National Heart and Lung Institute Imperial College, ICMS Royal Brompton Hospital, Guy Scadding Building, Dovehouse Street, London SW3 6LY, UK kim.fox@imperial.ac.uk.
authors.forename: Kim
authors.initials: K
authors.lastname: Fox
authors.affiliation: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.affiliation: National Heart and Lung Institute Imperial College, ICMS Royal Brompton Hospital, Guy Scadding Building, Dovehouse Street, London SW3 6LY, UK Département Hospitalo-Universitaire FIRE, Hôpital Bichat, Assistance Publique, Hôpitaux de Paris, Paris, France INSERM U-1148, Paris, France Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France.
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: Montreal Heart Institute Coordinating Center (MHICC), Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
authors.affiliation: 3rd Division of Cardiology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Tendera
authors.affiliation: Department of Cardiology and LTTA Centre, University Hospital of Ferrara, Ferrara, and Maria Cecilia Hospital, GVM Care & Research, E.S. Health Science Foundation, Cotignola, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ferrari
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000139:chemically induced*; D001552:Benzazepines / Q000009:adverse effects*; D001919:Bradycardia / Q000139:chemically induced*; D002317:Cardiovascular Agents / Q000009:adverse effects*; D003324:Coronary Artery Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D001552:Benzazepines; D002317:Cardiovascular Agents; D000077550:Ivabradine
keywords: Adverse event; Angina; Atrial fibrillation; Bradycardia; CAD; Ivabradine