Risk of stroke during long-term anticoagulant therapy in patients after myocardial infarction

Ann Neurol. 1996 Mar;39(3):301-7. doi: 10.1002/ana.410390306.


Myocardial infarction survivors have an increased risk of stroke, which is reduced with long-term anticoagulant therapy. However, an estimated 10-times increase in risk of bleeding during such treatment has been reported. We evaluated the risk of stroke in patients after a myocardial infarction and examined the relationship of the risk of intracranial hemorrhage or cerebral infarction and the intensity of anticoagulant therapy. The study population consisted of 3,404 post-myocardial infarction patients who took part in a randomized, double-blind, placebo-controlled trial. Patients were randomized to treatment with anticoagulants (international normalized ratio range, 2.8-4.8) or matching placebo. Mean follow-up was more than 3 years. The incidence of stroke analyzed on "intention-to-treat" was 0.7 per 100 patient-years in the anticoagulant patients against 1.2 in placebo, a hazard ratio of 0.60, with 95% confidence interval of 0.40 to 0.90. In the anticoagulation group, 15 patients had cerebral infarction and 17 an intracranial bleeding, 3 of which occurred after withdrawal of treatment. In the placebo group, the numbers were 43 and 2. Of the 14 intracranial bleeds during anticoagulation, 6 occurred at an international normalized ratio between 3.0 and 4.0 and 8 at greater than 4.0. These results confirm that long-term anticoagulant therapy substantially reduces the risk of stroke in post-myocardial infarction patients. The increased risk of bleeding complications associated with anticoagulant therapy is offset by a marked reduction in ischemic events. The risk of intracranial bleeding is directly related to the intensity of anticoagulant treatment.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / epidemiology
  • Cerebral Infarction / chemically induced
  • Cerebral Infarction / epidemiology
  • Cerebrovascular Disorders / epidemiology*
  • Cerebrovascular Disorders / etiology
  • Cerebrovascular Disorders / prevention & control*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Myocardial Infarction / complications
  • Myocardial Infarction / drug therapy*
  • Placebos
  • Proportional Hazards Models
  • Risk Factors


  • Anticoagulants
  • Placebos