Objective: To assess independent predictors of hemorrhage in 651 anticoagul
ated patients. Background: An excess incidence of major bleeding (7% per ye
ar) in patients with nondisabling cerebral ischemia of presumed arterial or
igin treated with oral anticoagulation led to early termination of the Stro
ke Prevention In Reversible Ischemia Trial (SPIRIT), Methods: The relations
hip between known risk factors and hemorrhage was assessed by univariate an
d multivariate analyses. We compared the risk factors with those in 225 pat
ients anticoagulated because of cerebral ischemia with atrial fibrillation
in the European Atrial Fibrillation Trial (EAFT), Results: Leukoaraiosis (h
azard ratio [HR] 2.7, 95% confidence interval [CI] 1.4 to 5.3) and age olde
r than 65 years (HR 1.9, 95% CI 1.0 to 3.4) were independent predictors of
all anticoagulation-related hemorrhages in SPIRIT, The incidence of intracr
anial bleeding in SPIRIT was 3.7% per year; this incidence increased by a f
actor of 1.37 for each 0.5 unit international normalized ratio (INR), Patie
nts with cerebral ischemia of presumed arterial origin had a 19 times (95%
CI 2.4 to 150) higher risk of intracranial hemorrhages than those with atri
al fibrillation after correcting for baseline differences between SPIRIT an
d EAFT patients. Conclusions: In addition to the intensity of anticoagulati
on, leukoaraiosis and age older than 65 years are independent risk factors
for bleeding in patients anticoagulated because of cerebral ischemia of pre
sumed arterial origin. These patients have a higher inherent risk of antico
agulation-related intracranial hemorrhages than patients with atrial fibril
lation.