title: Incidence, source, determinants, and prognostic impact of major bleeding in outpatients with stable coronary artery disease.
abstract: BACKGROUND
  Although there is evidence that patients who experience major bleeding after an acute coronary event are at higher risk of death in the months after the event, the incidence and impact on outcome of bleeding beyond 1 year of follow-up in patients with stable coronary artery disease (CAD) are largely unknown.
  
  
  OBJECTIVE
  The goal of this study was to assess the incidence, source, determinants, and prognostic impact of major bleeding in stable CAD.
  
  
  METHODS
  We prospectively included 4,184 consecutive CAD outpatients who were free from any myocardial infarction (MI) or coronary revascularization for >1 year at inclusion. Follow-up was performed at 2 years, with major bleeding defined as a type ≥3 bleed using the Bleeding Academic Research Consortium (BARC) definition.
  
  
  RESULTS
  There were 51 major bleeding events during follow-up (0.6%/year). Most events were BARC type 3a bleeds with 12 fatal bleeds (type 5). In most cases (54.9%), the site of bleeding was gastrointestinal. Major bleeding was significantly associated with mortality (adjusted hazard ratio: 2.89; 95% confidence intervals: 1.73 to 4.83; p < 0.0001). The increased risk of bleeding associated with vitamin K antagonist (VKA) treatment was particularly evident when VKA was combined with an antiplatelet therapy (APT). In contrast, the risk of cardiovascular death, MI, or nonhemorrhagic stroke did not differ in patients who received VKA + APT versus patients on VKA alone.
  
  
  CONCLUSIONS
  In patients with stable CAD (i.e., >1 year, with no acute events), major bleeding events are rare, but such events are an independent predictor of death. When oral anticoagulation is required, concomitant APT should not be prescribed in the absence of a recent cardiovascular event.
authors.affiliation: Centre Hospitalier Universitaire de Caen, Caen, France; Faculté de Médecine de Caen, Caen, France.
authors.forename: Martial
authors.initials: M
authors.lastname: Hamon
authors.affiliation: Centre Hospitalier Régional et Universitaire de Lille, Lille, France; Inserm U744, Institut Pasteur de Lille, Université Lille Nord de France, Lille, France; Faculté de Médecine de Lille, Lille, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Lemesle
authors.affiliation: Centre Hospitalier de Dunkerque, Dunkerque, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tricot
authors.affiliation: Polyclinique du Bois, Lille, France.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Meurice
authors.affiliation: Centre Hospitalier Régional et Universitaire de Lille, Lille, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Deneve
authors.affiliation: Centre Hospitalier de Boulogne-Sur-Mer, Boulogne-Sur-Mer, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Dujardin
authors.affiliation: Polyclinique Vauban, Valenciennes, France.
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Brufau
authors.affiliation: Polyclinique du Bois, Lille, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Bera
authors.affiliation: Centre Hospitalier Régional et Universitaire de Lille, Lille, France; Inserm U744, Institut Pasteur de Lille, Université Lille Nord de France, Lille, France; Faculté de Médecine de Lille, Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lamblin
authors.affiliation: Centre Hospitalier Régional et Universitaire de Lille, Lille, France; Inserm U744, Institut Pasteur de Lille, Université Lille Nord de France, Lille, France; Faculté de Médecine de Lille, Lille, France. Electronic address: christophe.bauters@chru-lille.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Bauters
mesh_terms: D000284:Administration, Oral; D000368:Aged; D003324:Coronary Artery Disease / Q000150:complications* / Q000453:epidemiology / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000150:complications* / Q000453:epidemiology / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010045:Outpatients; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D013997:Time Factors; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors
chemical_list: D010975:Platelet Aggregation Inhibitors; D014812:Vitamin K
keywords: antiplatelet agent; coronary artery disease; major bleeding; oral anticoagulant; outcome; vitamin K antagonist