Risk of stroke during long-term anticoagulant therapy in patients after myocardial infarction.
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.
Azar
A J
AJ
Department of Clinical Epidemiology, University Hospital Dijkzigt, Rotterdam, The Netherlands.
Koudstaal
P J
PJ
Wintzen
A R
AR
van Bergen
P F
PF
Jonker
J J
JJ
Deckers
J W
JW
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D002544:Cerebral Infarction / Q000139:chemically induced / Q000453:epidemiology; D002561:Cerebrovascular Disorders / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy*; D010919:Placebos; D016016:Proportional Hazards Models; D012307:Risk Factors
D000925:Anticoagulants; D010919:Placebos