FIXED MINIDOSE WARFARIN AND ASPIRIN ALONE AND IN COMBINATION VS ADJUSTED-DOSE WARFARIN FOR STROKE PREVENTION IN ATRIAL-FIBRILLATION - 2ND COPENHAGEN ATRIAL-FIBRILLATION, ASPIRIN, AND ANTICOAGULATION STUDY

Background: Despite the efficacy of warfarin sodium therapy for stroke prevention in atrial fibrillation, many physicians hesitate to prescr ibe it to elderly patients because of the risk for bleeding complicati ons and because of inconvenience for the patients. Methods: The Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study wa s a randomized, controlled trial examining the following therapies: wa rfarin sodium, 1.25 mg/d; warfarin sodium, 1.25 mg/d, plus aspirin, 30 0 mg/d; and aspirin, 300 mg/d. These were compared with adjusted-dose warfarin therapy (international normalized ratio of prothrombin time [ INR], 2.0-3.0). Stroke or a systemic thromboembolic event was the prim ary outcome event. Transient ischemic attack, acute myocardial infarct ion, and death were secondary events. Data were handled as survival da ta, and risk factors were identified using the Cox proportional hazard s model. The trial was scheduled for 6 years from May 1, 1993, but due to scientific evidence of inefficiency of low-intensity warfarin plus aspirin therapy from another study, our trial was prematurely termina ted on October 2, 1996. Results: We included 677 patients (median age, 74 years). The cumulative primary event rate after 1 year was 5.8% in patients receiving minidose warfarin; 7.2%, warfarin plus aspirin; 3. 6%, aspirin; and 2.8%, adjusted-dose warfarin (P=.67). After 3 years, no difference among the groups was seen. Major bleeding events were ra re. Conclusions: Although the difference was insignificant, adjusted-d ose warfarin seemed superior to minidose warfarin and to warfarin plus aspirin after 1 year of treatment. The results do not justify a chang e in the current recommendation of adjusted-dose warfarin (INR, 2.0-3. 0) for stroke prevention in atrial fibrillation.