Major bleeding during anticoagulation after cerebral ischemia: patterns and risk factors. Stroke Prevention In Reversible Ischemia Trial (SPIRIT). European Atrial Fibrillation Trial (EAFT) study groups.

OBJECTIVE

To assess independent predictors of hemorrhage in 651 anticoagulated patients.

BACKGROUND

An excess incidence of major bleeding (7% per year) in patients with nondisabling cerebral ischemia of presumed arterial origin treated with oral anticoagulation led to early termination of the Stroke Prevention In Reversible Ischemia Trial (SPIRIT).

METHODS

The relationship between known risk factors and hemorrhage was assessed by univariate and multivariate analyses. We compared the risk factors with those in 225 patients anticoagulated because of cerebral ischemia with atrial fibrillation in the European Atrial Fibrillation Trial (EAFT).

RESULTS

Leukoaraiosis (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.4 to 5.3) and age older 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 intracranial bleeding in SPIRIT was 3.7% per year; this incidence increased by a factor of 1.37 for each 0.5 unit international normalized ratio (INR). Patients 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 atrial fibrillation after correcting for baseline differences between SPIRIT and EAFT patients.

CONCLUSIONS

In addition to the intensity of anticoagulation, leukoaraiosis and age older than 65 years are independent risk factors for bleeding in patients anticoagulated because of cerebral ischemia of presumed arterial origin. These patients have a higher inherent risk of anticoagulation-related intracranial hemorrhages than patients with atrial fibrillation.