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3至6个月的全剂量华法林抗凝治疗。然而，采用这种治疗方案的患者在停止抗凝治疗后立即出现血栓复发、再住院和死亡率的高发生率。对于疾病复发风险平均的患者，以及由于抗凝遗传缺陷（如factor V Leiden突变）而风险升高的患者，都是如此。不幸的是，目前没有临床治疗方案被证明有足够的益处来支持长期预防。特别是，长期使用全剂量华法林与出血风险显著增加有关。相比之下，虽然靶向低剂量华法林（INR 1.5-2.0）长期治疗是安全的，但这种方法在预防静脉血栓栓塞性疾病复发中的有效性仍未得到检验。预防静脉血栓栓塞复发（Prevention）试验将评估低剂量华法林长期治疗在静脉血栓栓塞（VTE）二级预防中的疗效。有特发性静脉血栓形成病史并完成标准疗程抗凝治疗的患者将被纳入一项随机、双盲、安慰剂对照试验，比较常规治疗加靶向低剂量华法林与常规治疗加安慰剂长达4年。试验终点将包括复发性静脉血栓栓塞、大出血发作和总患者人群的全因死亡率，以及Leiden因子V患者的全因死亡率。预防试验的潜在临床影响是广泛的，因为阳性结果将强烈支持静脉血栓形成患者的慢性低强度抗凝治疗，这些患者在停止标准门诊抗凝治疗后有复发风险。

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 increased 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.