Ridker Paul M, Goldhaber Samuel Z, Danielson Ellie, Rosenberg Yves, Eby Charles S, Deitcher Steven R, Cushman Mary, Moll Stephan, Kessler Craig M, Elliott C Gregory, Paulson Rolf, Wong Turnly, Bauer Kenneth A, Schwartz Bruce A, Miletich Joseph P, Bounameaux Henri, Glynn Robert J
Center for Cardiovascular Disease Prevention and the Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston 02215, USA.
N Engl J Med. 2003 Apr 10;348(15):1425-34. doi: 10.1056/NEJMoa035029. Epub 2003 Feb 24.
Standard therapy to prevent recurrent venous thromboembolism includes 3 to 12 months of treatment with full-dose warfarin with a target international normalized ratio (INR) between 2.0 and 3.0. However, for long-term management, no therapeutic agent has shown an acceptable benefit-to-risk ratio.
Patients with idiopathic venous thromboembolism who had received full-dose anticoagulation therapy for a median of 6.5 months were randomly assigned to placebo or low-intensity warfarin (target INR, 1.5 to 2.0). Participants were followed for recurrent venous thromboembolism, major hemorrhage, and death.
The trial was terminated early after 508 patients had undergone randomization and had been followed for up to 4.3 years (mean, 2.1). Of 253 patients assigned to placebo, 37 had recurrent venous thromboembolism (7.2 per 100 person-years), as compared with 14 of 255 patients assigned to low-intensity warfarin (2.6 per 100 person-years), a risk reduction of 64 percent (hazard ratio, 0.36 [95 percent confidence interval, 0.19 to 0.67]; P<0.001). Risk reductions were similar for all subgroups, including those with and those without inherited thrombophilia. Major hemorrhage occurred in two patients assigned to placebo and five assigned to low-intensity warfarin (P=0.25). Eight patients in the placebo group and four in the group assigned to low-intensity warfarin died (P=0.26). Low-intensity warfarin was thus associated with a 48 percent reduction in the composite end point of recurrent venous thromboembolism, major hemorrhage, or death. According to per-protocol and as-treated analyses, the reduction in the risk of recurrent venous thromboembolism was between 76 and 81 percent.
Long-term, low-intensity warfarin therapy is a highly effective method of preventing recurrent venous thromboembolism.
预防复发性静脉血栓栓塞的标准疗法包括使用全剂量华法林治疗3至12个月，目标国际标准化比值（INR）在2.0至3.0之间。然而，对于长期管理而言，尚无治疗药物显示出可接受的效益风险比。
接受全剂量抗凝治疗中位数为6.5个月的特发性静脉血栓栓塞患者被随机分配至安慰剂组或低强度华法林组（目标INR为1.5至2.0）。对参与者进行复发性静脉血栓栓塞、大出血和死亡情况的随访。
在508例患者完成随机分组并随访长达4.3年（平均2.1年）后，该试验提前终止。在分配至安慰剂组的253例患者中，37例发生复发性静脉血栓栓塞（每100人年7.2例），而在分配至低强度华法林组的255例患者中，有14例发生（每100人年2.6例），风险降低了64%（风险比，0.36[95%置信区间，0.19至0.67]；P<0.001）。所有亚组的风险降低情况相似，包括有和没有遗传性血栓形成倾向的亚组。安慰剂组有2例患者发生大出血，低强度华法林组有5例（P=0.25）。安慰剂组有8例患者死亡，低强度华法林组有4例（P=0.26）。因此，低强度华法林与复发性静脉血栓栓塞、大出血或死亡的复合终点降低48%相关。根据符合方案分析和实际治疗分析，复发性静脉血栓栓塞风险降低76%至81%。
长期低强度华法林治疗是预防复发性静脉血栓栓塞的一种高效方法。
