title: Bleeding after initiation of multiple antithrombotic drugs, including triple therapy, in atrial fibrillation patients following myocardial infarction and coronary intervention: a nationwide cohort study.
abstract: BACKGROUND
  Uncertainty remains over optimal antithrombotic treatment of patients with atrial fibrillation presenting with myocardial infarction and/or undergoing percutaneous coronary intervention. We investigated the risk and time frame for bleeding following myocardial infarction/percutaneous coronary intervention in patients with atrial fibrillation according to antithrombotic treatment.
  
  
  RESULTS
  Patients with atrial fibrillation and admitted with myocardial infarction or for percutaneous coronary intervention between 2000 and 2009 (11 480 subjects, mean age 75.6 years [SD ±10.3], males 60.9%) were identified by individual level linkage of nationwide registries in Denmark. Fatal or nonfatal (requiring hospitalization) bleeding was determined according to antithrombotic treatment regimen: triple therapy (TT) with vitamin K antagonist (VKA)+aspirin+clopidogrel, VKA+antiplatelet, and dual antiplatelet therapy with aspirin+clopidogrel. We calculated crude incidence rates and adjusted hazard ratios by Cox regression models. Within 1 year, 728 bleeding events were recorded (6.3%); 79 were fatal (0.7%). Within 30 days, rates were 22.6, 20.3, and 14.3 bleeding events per 100 person-years for TT, VKA+antiplatelet, and dual antiplatelet therapy, respectively. Both early (within 90 days) and delayed (90-360 days) bleeding risk with TT exposure in relation to VKA+antiplatelet was increased; hazard ratio 1.47 (1.04;2.08) and 1.36 (0.95;1.95), respectively. No significant difference in thromboembolic risk was observed for TT versus VKA+antiplatelet; hazard ratio, 1.15 (0.95;1.40).
  
  
  CONCLUSIONS
  High risk of bleeding is immediately evident with TT after myocardial infarction/percutaneous coronary intervention in patients with atrial fibrillation. A continually elevated risk associated with TT indicates no safe therapeutic window, and TT should only be prescribed after thorough bleeding risk assessment of patients.
authors.affiliation: Department of Cardiology, Post 635, Copenhagen University Hospital Gentofte, Niels Andersens Vej 65, 2900 Hellerup, Denmark. mortenlamberts@gmail.com
authors.forename: Morten
authors.initials: M
authors.lastname: Lamberts
authors.forename: Jonas Bjerring
authors.initials: JB
authors.lastname: Olesen
authors.forename: Martin Huth
authors.initials: MH
authors.lastname: Ruwald
authors.forename: Carolina Malta
authors.initials: CM
authors.lastname: Hansen
authors.forename: Deniz
authors.initials: D
authors.lastname: Karasoy
authors.forename: Søren Lund
authors.initials: SL
authors.lastname: Kristensen
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.forename: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
authors.forename: Gunnar Hilmar
authors.initials: GH
authors.lastname: Gislason
authors.forename: Morten Lock
authors.initials: ML
authors.lastname: Hansen
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality; D000077144:Clopidogrel; D015331:Cohort Studies; D015897:Comorbidity; D003718:Denmark / Q000453:epidemiology; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D006470:Hemorrhage / Q000139:chemically induced* / Q000401:mortality* / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000628:therapy*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D012042:Registries / Q000706:statistics & numerical data; D012307:Risk Factors; D020521:Stroke / Q000401:mortality; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D014812:Vitamin K / Q000037:antagonists & inhibitors
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D014812:Vitamin K; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin