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 i s high, especially among the elderly. Fixed minidose warfarin is effec tive in preventing venous thromboembolism with low risk of bleeding an d no need for frequent clinical monitoring. Patients > 60 years with n onrheumatic AF were randomized in an open-labeled trial to receive fix ed minidose warfarin (1.25 mg/day) or standard adjusted-dose warfarin (International Normalized Patio [INR] between 2.0 and 3.0). Primary ou tcome events were ischemic stroke, peripheral or visceral embolism, ce rebral or fatal bleeding, and vascular death. Secondary end points wer e major bleeding, myocardial infarction, and death. This study was dis continued before completion in light of publication of the Stroke Prev ention in Atrial Fibrillation III trial, which indicated that low-inte nsity fixed-dose warfarin treatment (i.e., INP < 1.5) was insufficient for stroke prevention in high-risk patients with nonrheumatic AF. Fro m a total of 1,209 considered patients, 303 were randomized to be stud ied (150 in the minidose group and 153 in the adjusted-dose group). Me an follow-up was 14.5 months. The rate of cumulative primary events wa s 11.1% (95% confidence intervals [CI] 4.0 to 18.2) in the fixed minid ose group and 6.1% (95% CI 1.1 to 11.1) in the adjusted-dose group (p = 0.29). The rate of ischemic stroke was significantly higher in the m inidose group (3.7% vs 0% per year, p = 0.025). Major bleedings were m ore frequent in standard treatment group (2.6% vs 1% per year, p = 0.1 9). Most thromboembolic complications occurred at INRs < 1.2, whereas the majority of hemorrhages occurred at INRs > 3.0. No significant dif ference in primary outcome events was observed in the abbreviated stud y. However, the significantly increased occurrence of ischemic stroke in the fixed minidose warfarin group suggests that this regimen does n ot protect patients with nonrheumatic AF. (C)1998 by Excerpta Medica, Inc.