Effect of oral antiplatelet agents on major bleeding in users of coumarins

Thromb Haemost. 2008 Dec;100(6):1076-83. doi: 10.1160/th08-05-0290.


Treatment with vitamin K antagonists (coumarins) is associated with an increased risk of bleeding. In order to elucidate the bleeding risk of users of antiplatelet drugs among users of coumarins, we assessed the odds ratio of major bleeding associated with use of antiplatelet drugs in users of the coumarins acenocoumarol and phenprocoumon. We used data from a Dutch record linkage system, including pharmacy and linked hospitalization records for approximately two million subjects, to conduct a nested case control study in a cohort of new users of coumarins. Cases were patients who were hospitalized with a primary diagnosis of major bleeding while taking coumarin and were matched with up to four control subjects. Conditional logistic regression analysis was used to determine ORs and 95% confidence intervals (CI). We identified 1848 case patients who were matched to 5818 controls. Users of clopidogrel or aspirin showed a significantly increased risk of hospitalization because of major bleeding (OR 2.9, 95% CI 1.2-6.9 and OR 1.6, 95% CI 1.3-1.9, respectively), whereas users of dipyridamole and combinations of antiplatelet drugs showed a strong trend (OR 1.5, 95% CI 1.0-2.3 and OR 1.8, 95 % CI 1.0-3.3, respectively). In all cases, the risks were greater for upper gastrointestinal bleedings than for other bleedings. In conclusion, the use of any antiplatelet drug increases the risk of hospitalization for major bleeding among users of coumarins. Concurrent use of clopidogrel or dipyridamole and coumarins is probably not safer than concurrent use of aspirin and coumarins.

MeSH terms

  • Acenocoumarol / adverse effects
  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Anticoagulants / adverse effects*
  • Aspirin / adverse effects
  • Blood Coagulation / drug effects*
  • Case-Control Studies
  • Clopidogrel
  • Coumarins / adverse effects*
  • Dipyridamole / adverse effects
  • Drug Therapy, Combination
  • Female
  • Gastrointestinal Hemorrhage / blood
  • Gastrointestinal Hemorrhage / chemically induced
  • Hemorrhage / blood
  • Hemorrhage / chemically induced*
  • Hospitalization
  • Humans
  • Logistic Models
  • Male
  • Medical Records Systems, Computerized
  • Middle Aged
  • Netherlands
  • Odds Ratio
  • Phenprocoumon / adverse effects
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects*
  • Risk Assessment
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives
  • Vitamin K / antagonists & inhibitors*


  • Anticoagulants
  • Coumarins
  • Platelet Aggregation Inhibitors
  • Vitamin K
  • Dipyridamole
  • Clopidogrel
  • Acenocoumarol
  • Ticlopidine
  • Phenprocoumon
  • Aspirin