Effectiveness of fixed minidose warfarin in the prevention of thromboembolism and vascular death in nonrheumatic atrial fibrillation

Adjusted-dose warfarin is effective for stroke prevention in patients with nonrheumatic atrial fibrillation (AF), but the risk of bleeding is high, especially among the elderly. Fixed minidose warfarin is effective in preventing venous thromboembolism with low risk of bleeding and no need for frequent clinical monitoring. Patients >60 years with nonrheumatic AF were randomized in an open-labeled trial to receive fixed minidose warfarin (1.25 mg/day) or standard adjusted-dose warfarin (International Normalized Ratio [INR] between 2.0 and 3.0). Primary outcome events were ischemic stroke, peripheral or visceral embolism, cerebral or fatal bleeding, and vascular death. Secondary end points were major bleeding, myocardial infarction, and death. This study was discontinued before completion in light of publication of the Stroke Prevention in Atrial Fibrillation III trial, which indicated that low-intensity fixed-dose warfarin treatment (i.e., INR 3.0. No significant difference in primary outcome events was observed in the abbreviated study. However, the significantly increased occurrence of ischemic stroke in the fixed minidose warfarin group suggests that this regimen does not protect patients with nonrheumatic AF.