Background: The Stroke Prevention in Atrial Fibrillation II study compared warfarin vs aspirin for stroke prevention in atrial fibrillation. Bleeding complications importantly detracted from warfarin's net effectiveness, particularly among older patients.
Objectives: To analyze bleeding complications according to assigned therapy. To identify risk factors for bleeding during anticoagulation.
Methods: Eleven hundred patients (mean age, 70 years) were randomized to 325 mg of aspirin daily (enteric coated) vs warfarin (target prothrombin time ratio, 1.3 to 1.8; approximate international normalized ratio, 2.0 to 4.5). Major hemorrhages were defined prospectively.
Results: The rate of major bleeding while receiving warfarin was 2.3% per year (95% confidence interval [CI], 1.7 to 3.2) vs 1.1% per year (95% CI, 0.7 to 1.8) while receiving aspirin (relative risk, 2.1; 95% CI, 1.1 to 3.1; P = .02). Intracranial hemorrhage occurred at 0.9% per year (95% CI, 0.5 to 1.5) with warfarin and 0.3% per year (95% CI, 0.1 to 0.8) with aspirin (relative risk, 2.4; P = .08). Age (P = .006), increasing number of prescribed medications (P = .007), and intensity of anticoagulation (P = .02) were independent risks for bleeding at any site during anticoagulation. The rate of major hemorrhage was 1.7% per year in patients aged 75 years or younger who received anticoagulation vs 4.2% per year in older patients (relative risk, 2.6, P = .009); rates by age for intracranial bleeding were 0.6% per year and 1.8% per year, respectively (P = .05).
Conclusion: Advancing age and more intense anticoagulation increase the risk of major hemorrhage in patients given warfarin for stroke prevention.