[The efficacy and safety of antithrombotic therapy with warfarin in nonrheumatic atrial fibrillation].

OBJECTIVE: To identify the optimal intensity of anticoagulation with warfarin in patients with nonvalvular atrial fibrillation by studying the relation between the thromboembolic and hemorrhagic events.

METHODS: Nonvalvular atrail fibrillation patients randomized to receive adjusted-dose warfarin [international normalized ratio (INR) 2.0 to 3.0] were included. The initial dose of warfarin was 2 mg and the dose was then adjusted to target at INR 2.0-3.0. Thromboembolic events and bleeding events were identified during follow-up.

RESULTS: Of the 335 patients, 204 (60.9%) were male. Mean age was (62.6 +/- 10.3) years. Sixty-six percent of all the patients had at least one risk factor for thromboembolism. The median follow-up period was 19 months (range 2-24 months). Among the 3482 INRs measured during the study, 2378 were in the target range. Of the 19 thromboembolic events occurred during warfarin therapy, 15 occurred with INR less than 2.0. The independent risk factors for thromboembolic events during warfarin therapy were age > 75 years, history of stroke, left ventricular ejection fraction (LVEF) < 0.40 and INR > 2.0. The incidence of bleeding events were 6.9%, including 5 cases (1.5%) of minor bleeding and 18 cases (5.4%) of major bleeding. The independent risk factors for the hemorrhage in warfarin treatment are age > 75 years, systolic blood pressure > or = 160 mm Hg, elevated serum creatinine level INR > 3.0. INR of 2.0 to 3.0 was associated with the lowest combined rate of bleeding and thromboembolism.

CONCLUSIONS: INR > 3.0 should be avoided to minimize the bleeding complications. Under intense monitoring, adjusted-dose warfarin (INR 2.0 - 3.0) is effective and safe for the moderate to high risk nonvalvular atrial fibrillation patients.