Bleeding complications associated with combinations of aspirin, thienopyridine derivatives, and warfarin in elderly patients following acute myocardial infarction

Arch Intern Med. 2005 Apr 11;165(7):784-9. doi: 10.1001/archinte.165.7.784.


Background: Combinations of aspirin with thienopyridine derivatives (clopidogrel bisulfate or ticlopidine hydrochloride) and/or warfarin sodium are increasingly being used in various cardiac conditions. However, little is known about the bleeding risks associated with these combinations, particularly in elderly individuals at the population level. This study estimates the bleeding risks associated with combinations of aspirin, thienopyridine derivatives, and warfarin in elderly patients.

Methods: We conducted a population-based observational cohort study using linked administrative databases. A total of 21,443 elderly survivors of acute myocardial infarction between 1996 and 2000 were studied. Patients were divided into 5 groups according to drug exposure: aspirin alone, warfarin alone, aspirin plus a thienopyridine derivative (antiplatelet combination), aspirin plus warfarin (anticoagulant combination), and aspirin plus warfarin plus a thienopyridine derivative (3-drug combination). Hospitalizations for bleeding events were examined.

Results: Hospitalizations for bleeding were observed in 1428 patients (7%). Compared with rates of patients receiving aspirin alone (0.03 per patient-year), rates of bleeding were higher among patients receiving the antiplatelet combination (0.07 per patient-year), the anticoagulant combination (0.08 per patient-year), and the 3-drug combination (0.09 per patient-year). Compared with aspirin alone, the adjusted odds ratios (95% confidence intervals) for bleeding were 1.65 (1.02-2.73) for patients receiving the antiplatelet combination and 1.92 (1.28-2.87) for patients receiving the anticoagulant combination. Only 1 of 141 patients in the 3-drug combination group had a bleeding event.

Conclusion: In practice, antiplatelet and anticoagulant combinations lead to modest increases in bleeding risk in elderly patients, but the overall risk is small.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects*
  • Aspirin / administration & dosage
  • Aspirin / adverse effects*
  • Case-Control Studies
  • Clopidogrel
  • Cohort Studies
  • Drug Therapy, Combination
  • Female
  • Hemorrhage / chemically induced*
  • Humans
  • Male
  • Myocardial Infarction / drug therapy
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects*
  • Risk Assessment
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects*
  • Ticlopidine / analogs & derivatives*
  • Warfarin / administration & dosage
  • Warfarin / adverse effects*


  • Anticoagulants
  • Platelet Aggregation Inhibitors
  • Warfarin
  • Clopidogrel
  • Ticlopidine
  • Aspirin