PREVENT: PREVENTION OF RECURRENT VENOUS THROMBOEMBOLISM

深静脉血栓形成和肺栓塞患者的标准治疗通常包括全剂量华法林抗凝3-6个月。然而，接受该方案的患者在停止抗凝后的几年内，血栓复发、再次住院和死亡率很高。对于疾病复发风险平均的患者，以及由于存在遗传性抗凝缺陷(如因子V莱顿突变)而风险增加的患者，情况也是如此。不幸的是，目前还没有可用的临床方案被证明有足够的益处来支持长期预防。特别值得一提的是，长期使用全剂量华法林可显著增加出血风险。相反，尽管靶向小剂量华法林(INR 1.5-2.0)对于长期治疗是安全的，但这种方法在预防复发静脉血栓栓塞性疾病方面的有效性仍未得到检验。预防静脉血栓栓塞症(预防)试验将评估小剂量华法林长期治疗在静脉血栓栓塞症(VTE)二级预防中的效果。有记录在案的特发性静脉血栓形成史的患者完成了标准的抗凝治疗，他们将参加一项随机、双盲、安慰剂对照试验，比较常规护理加有针对性的小剂量华法林与常规护理加安慰剂，为期最长四年。试验终点将包括复发的静脉血栓栓塞症、大出血发作，以及所有导致死亡的患者群体和那些单独使用因子V莱顿的患者。预防试验的潜在临床影响是广泛的，因为阳性结果将有力地支持静脉血栓形成患者在停止标准门诊抗凝后有复发风险的慢性低强度抗凝。

Standard therapy for patients with deep venous thrombosis and pulmonary embolism typically includes anticoagulation for a 3 to 6 month period with full dose warfarin. However, patients following this regimen experience high rates of recurrent thrombosis, re-hospitalization, and mortality in the years immediately following cessation of anticoagulation. This is true for patients at average risk of disease recurrence, and for patients at elevated risk due to the presence of inherited defects of anticoagulation such as factor V Leiden mutation. Unfortunately, no clinical regimen currently available has proven to have sufficient benefit to support long term prophylaxis. In particular, full dose warfarin is associated with substantially incrased risks of hemorrhage when used on a long term basis. In contrast, while targeted low dose warfarin (INR 1.5-2.0) is safe for long term therapy, the efficacy of this approach in the prevention of recurrent venous thromboembolic disease has remained untested. The Prevention of Recurrent Venous Thromboembolism (PREVENT) trial will evaluate the efficacy of prolonged treatment with low dose warfarin in the secondary prevention of venous thromboembolism (VTE). Patients with a history of documented idiopathic venous thrombosis who have completed a standard course of anticoagulation therapy will be enrolled in a randomized, double-blind, placebo-controlled trial comparing usual care plus targeted low-dose warfarin to usual care plus placebo for a period of up to four years. Trial endpoints will include recurrent VTE, major bleeding episodes, and all cause mortality in the total patient population and separately in those patients with factor V Leiden. The potential clinical impact of the PREVENT trial is broad since a positive finding would strongly support chronic low-intensity anticoagulation among patients with venous thrombosis who are at risk for recurrence following cessation of standard outpatient anticoagulation.