Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement
Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement
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DOI：
10.1056/nejmoa035162
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发表时间：
2003-10-30
影响因子：
158.5
通讯作者：
Colwell, CW
中科院分区：
文献类型：
--
作者：
Francis, CW;Berkowitz, SD;Colwell, CW
背景：在之前的一项关于全膝关节置换术后静脉血栓栓塞预防的研究中，发现口服直接凝血酶抑制剂ximelagatran（不需要监测凝血或调整剂量）的疗效与华法林相似，剂量为24mg ximelagatran，每天两次。本研究的目的是确定更高剂量的ximelagatran是否优于华法林。方法：这项随机、双盲试验比较了7 - 12天口服ximelagatran的方案，剂量为24或36mg，每天两次，手术后早上开始，华法林治疗在手术当天晚上开始。静脉血栓栓塞的复合终点、各种原因的死亡和出血发生率是主要的结局指标。结果：在疗效分析的1851例患者中，口服ximelagatran剂量为36mg，每日两次，在静脉血栓栓塞和全因死亡的主要复合终点方面优于华法林（20.3%比27.6%；P=0.003）。两组在大出血（发生率分别为0.8%和0.7%）、围手术期出血指标、伤口特征或近端深静脉血栓形成、肺栓塞和死亡的复合次要终点方面无显著差异（2.7% vs. 4.1%； P=0.17）。结论：全膝关节置换术后晨起口服ximelagatran预防静脉血栓栓塞的效果优于华法林。两种药物的出血性并发症发生率相似。
BACKGROUND:In a previous study of the prevention of venous thromboembolism after total knee replacement, the efficacy of ximelagatran, an oral direct thrombin inhibitor that does not require monitoring of coagulation or dose adjustment, was found to be similar to that of warfarin at a dose of 24 mg of ximelagatran twice daily. The purpose of the present study was to determine whether a higher dose of ximelagatran is superior to warfarin.METHODS:This randomized, double-blind trial compared a regimen of 7 to 12 days of oral ximelagatran, at a dose of 24 or 36 mg twice daily, starting the morning after surgery, with warfarin therapy started the evening of the day of surgery. The composite end point of venous thromboembolism and death from all causes and the incidence of bleeding were the primary outcome measures.RESULTS:Among the 1851 patients in the efficacy analysis, oral ximelagatran at a dose of 36 mg twice daily was superior to warfarin with respect to the primary composite end point of venous thromboembolism and death from all causes (20.3 percent vs. 27.6 percent; P=0.003). There were no significant differences between these two groups with respect to major bleeding (incidence, 0.8 percent and 0.7 percent, respectively), perioperative indicators of bleeding, wound characteristics, or the composite secondary end point of proximal deep-vein thrombosis, pulmonary embolism, and death (2.7 percent vs. 4.1 percent; P=0.17).CONCLUSIONS:The efficacy of oral ximelagatran, administered starting the morning after total knee replacement, was superior to that of warfarin for prevention of venous thromboembolism. Rates of hemorrhagic complications with the two drugs were similar.