华法林对非瓣膜病心房颤动抗栓的安全性和有效性研究

目的观察华法林对非瓣膜病心房颤动(房颤)患者抗凝治疗的有效性和安全性。方法在18个中心进行阿司匹林(150～160 mg/d)与调整剂量华法林组随机对照研究中选取患者。华法林初始剂量2 mg/d,目标国际标准化比值(INR)2.0～3.0(年龄≥75岁者为1.6～2.5),常规门诊随访,分析该组患者终点事件和出血事件的发生及与抗凝强度的关系。结果共335例患者随机服用华法林,男204例(60.9%),年龄(62.6±10.3)岁,随访2～24个月(中位数19个月)。华法林平均剂量(3.19±0.69)mg。共进行 INR 测定3482人次,其中2378次 INR(占68.3%)维持2.0～3.0。用药期间发生主要终点事件10例(2.7%),次要终点事件19例(5.7%)。服用华法林期间总出血发生率为23例(6.9%),其中严重出血5例(1.5%),轻微出血18例(5.4%);发生血栓栓塞事件(缺血性卒中及体循环栓塞)19例(5.4%),其中15例(4.5%)患者发生事件时的 INR<2.0。多因素 logistic 回归显示,抗凝出血和血栓栓塞事件的独立危险因素均为年龄>75岁,前者收缩压≥160mm Hg,血肌酐升高,INR>3.0;后者有卒中病史,左室射血分数<0.40%和 INR<2.0。结论中国人非瓣膜病房颤患者应用华法林抗凝 INR 维持在2.0～3.0是安全有效的,但应避免 INR>3.0,以最大限度减少出血并发症,尤其应严密监测高龄、合并心力衰竭和肾功能异常的患者。

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.