Minidose warfarin (5.8%), warfarin plus aspirin (7.2%), and aspirin (3.6%) did not significantly differ from adjusted-dose warfarin (2.8%) for stroke or systemic embolism at 1 year (P=0.67).
RCT (n=677)
randomized
Does fixed minidose warfarin, aspirin, or their combination prevent stroke or systemic thromboembolism compared to adjusted-dose warfarin in patients with atrial fibrillation?
Fixed minidose warfarin and aspirin, alone or in combination, did not show a significant difference in stroke prevention compared to adjusted-dose warfarin, supporting the continued recommendation of adjusted-dose warfarin for atrial fibrillation.
Absolute Event Rate: 5.8% vs 2.8%
p-value: p=0.67
BACKGROUND: Despite the efficacy of warfarin sodium therapy for stroke prevention in atrial fibrillation, many physicians hesitate to prescribe it to elderly patients because of the risk for bleeding complications and because of inconvenience for the patients. METHODS: The Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study was a randomized, controlled trial examining the following therapies: warfarin sodium, 1.25 mg/d; warfarin sodium, 1.25 mg/d, plus aspirin, 300 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 primary outcome event. Transient ischemic attack, acute myocardial infarction, and death were secondary events. Data were handled as survival data, and risk factors were identified using the Cox proportional hazards 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 terminated 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 rare. CONCLUSIONS: Although the difference was insignificant, adjusted-dose warfarin seemed superior to minidose warfarin and to warfarin plus aspirin after 1 year of treatment. The results do not justify a change in the current recommendation of adjusted-dose warfarin (INR, 2.0-3.0) for stroke prevention in atrial fibrillation.
Gulløv et al. (1998) conducted an RCT in Atrial fibrillation (n=677). Minidose warfarin alone, minidose warfarin plus aspirin, or aspirin alone vs. Adjusted-dose warfarin (INR 2.0-3.0) was evaluated on Stroke or a systemic thromboembolic event (p=0.67). Minidose warfarin (5.8%), warfarin plus aspirin (7.2%), and aspirin (3.6%) did not significantly differ from adjusted-dose warfarin (2.8%) for stroke or systemic embolism at 1 year (P=0.67).