Bleeding after initiation of multiple antithrombotic drugs, including triple therapy, in atrial fibrillation patients following myocardial infarction and coronary intervention: a nationwide cohort study

Circulation. 2012 Sep 4;126(10):1185-93. doi: 10.1161/CIRCULATIONAHA.112.114967. Epub 2012 Aug 6.

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.

Methods and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / drug therapy
  • Acute Coronary Syndrome / mortality
  • Aged
  • Aged, 80 and over
  • Angioplasty, Balloon, Coronary*
  • Aspirin / administration & dosage
  • Aspirin / adverse effects
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / mortality
  • Clopidogrel
  • Cohort Studies
  • Comorbidity
  • Denmark / epidemiology
  • Drug Therapy, Combination / adverse effects
  • Female
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / adverse effects*
  • Hemorrhage / chemically induced*
  • Hemorrhage / mortality*
  • Hemorrhage / prevention & control
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / mortality
  • Myocardial Infarction / therapy*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects
  • Registries / statistics & numerical data
  • Risk Factors
  • Stroke / mortality
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives
  • Vitamin K / antagonists & inhibitors

Substances

  • Fibrinolytic Agents
  • Platelet Aggregation Inhibitors
  • Vitamin K
  • Clopidogrel
  • Ticlopidine
  • Aspirin