Kearon Clive, Ginsberg Jeffrey S, Kovacs Michael J, Anderson David R, Wells Philip, Julian Jim A, MacKinnon Betsy, Weitz Jeffrey I, Crowther Mark A, Dolan Sean, Turpie Alexander G, Geerts William, Solymoss Susan, van Nguyen Paul, Demers Christine, Kahn Susan R, Kassis Jeannine, Rodger Marc, Hambleton Julie, Gent Michael
McMaster University, Hamilton, Ont.
N Engl J Med. 2003 Aug 14;349(7):631-9. doi: 10.1056/NEJMoa035422.
Warfarin is very effective in preventing recurrent venous thromboembolism but is also associated with a substantial risk of bleeding. After three months of conventional warfarin therapy, a lower dose of anticoagulant medication may result in less bleeding and still prevent recurrent venous thromboembolism.
We conducted a randomized, double-blind study, in which 738 patients who had completed three or more months of warfarin therapy for unprovoked venous thromboembolism were randomly assigned to continue warfarin therapy with a target international normalized ratio (INR) of 2.0 to 3.0 (conventional intensity) or a target INR of 1.5 to 1.9 (low intensity). Patients were followed for an average of 2.4 years.
Of 369 patients assigned to low-intensity therapy, 16 had recurrent venous thromboembolism (1.9 per 100 person-years), as compared with 6 of 369 assigned to conventional-intensity therapy (0.7 per 100 person-years; hazard ratio, 2.8; 95 percent confidence interval, 1.1 to 7.0). A major bleeding episode occurred in nine patients assigned to low-intensity therapy (1.1 events per 100 person-years) and eight patients assigned to conventional-intensity therapy (0.9 event per 100 person-years; hazard ratio, 1.2; 95 percent confidence interval, 0.4 to 3.0). There was no significant difference in the frequency of overall bleeding between the two groups (hazard ratio, 1.3; 95 percent confidence interval, 0.8 to 2.1).
Conventional-intensity warfarin therapy is more effective than low-intensity warfarin therapy for the long-term prevention of recurrent venous thromboembolism. The low-intensity warfarin regimen does not reduce the risk of clinically important bleeding.
华法林在预防复发性静脉血栓栓塞方面非常有效，但也伴有显著的出血风险。在进行三个月的传统华法林治疗后，较低剂量的抗凝药物可能会减少出血，同时仍能预防复发性静脉血栓栓塞。
我们进行了一项随机双盲研究，将738例因不明原因静脉血栓栓塞接受了三个月或更长时间华法林治疗的患者随机分为两组，一组继续接受华法林治疗，目标国际标准化比值（INR）为2.0至3.0（传统强度），另一组目标INR为1.5至1.9（低强度）。患者平均随访2.4年。
在分配到低强度治疗的369例患者中，有16例发生复发性静脉血栓栓塞（每100人年1.9例），而分配到传统强度治疗的369例患者中有6例发生（每100人年0.7例；风险比为2.8；95%置信区间为1.1至7.0）。分配到低强度治疗的9例患者发生了严重出血事件（每100人年1.1次事件），分配到传统强度治疗的8例患者发生了严重出血事件（每100人年0.9次事件；风险比为1.2；95%置信区间为0.4至3.0）。两组之间的总体出血频率无显著差异（风险比为1.3；95%置信区间为0.8至2.1）。
传统强度的华法林治疗在长期预防复发性静脉血栓栓塞方面比低强度华法林治疗更有效。低强度华法林治疗方案并不能降低具有临床意义的出血风险。
