Francis Charles W, Davidson Bruce L, Berkowitz Scott D, Lotke Paul A, Ginsberg Jeffrey S, Lieberman Jay R, Webster Anne K, Whipple James P, Peters Gary R, Colwell Clifford W
University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
Ann Intern Med. 2002 Oct 15;137(8):648-55. doi: 10.7326/0003-4819-137-8-200210150-00008.
Warfarin is used for prophylaxis of venous thromboembolism in patients undergoing total knee arthroplasty. However, it is associated with rates of deep venous thrombosis (DVT) of approximately 38% to 55% and requires routine coagulation monitoring and frequent dose adjustment. Ximelagatran, an oral direct thrombin inhibitor, has shown promising efficacy and tolerability in patients undergoing total hip or knee arthroplasty.
To compare the efficacy and safety of ximelagatran and warfarin for prophylaxis of venous thromboembolism after total knee arthroplasty.
Randomized, double-blind, parallel-group trial.
74 North American hospitals.
680 patients who had undergone total knee arthroplasty.
7 to 12 days of treatment with oral ximelagatran, 24 mg twice daily, starting on the morning after surgery, or warfarin (target international normalized ratio, 2.5 [range, 1.8 to 3.0]), starting on the evening of the day of surgery.
Principal end points were asymptomatic DVT on mandatory venography; symptomatic DVT confirmed by ultrasonography or venography; symptomatic, objectively proven pulmonary embolism; and bleeding. All were assessed by blinded adjudication locally and at a central study laboratory.
On central adjudication, incidence of venous thromboembolism was 19.2% (53 of 276 patients) in the ximelagatran group and 25.7% (67 of 261 patients) in the warfarin group (difference, -6.5 percentage points [95% CI, -13.5 to 0.6 percentage points]; P = 0.070). On local assessment, incidence was 25.4% in the ximelagatran group and 33.5% in the warfarin group (P = 0.043). In the ximelagatran and warfarin groups, respectively, major bleeding occurred in 1.7% and 0.9% of patients and minor bleeding occurred in 7.8% and 6.4% of patients. No variables related to bleeding differed significantly between the two groups.
For prophylaxis of venous thromboembolism, fixed-dose ximelagatran started the morning after total knee arthroplasty is well tolerated and at least as effective as warfarin, but it does not require coagulation monitoring or dose adjustment.
华法林用于全膝关节置换术患者静脉血栓栓塞的预防。然而，其深静脉血栓形成（DVT）发生率约为38%至55%，且需要常规凝血监测和频繁调整剂量。希美加群是一种口服直接凝血酶抑制剂，在全髋关节或膝关节置换术患者中已显示出有前景的疗效和耐受性。
比较希美加群和华法林在全膝关节置换术后预防静脉血栓栓塞的疗效和安全性。
随机、双盲、平行组试验。
74家北美医院。
680例行全膝关节置换术的患者。
术后次日早晨开始口服希美加群，24mg，每日2次，共治疗7至12天；或术后当日晚上开始使用华法林（目标国际标准化比值为2.5[范围1.8至3.0]）。
主要终点为强制静脉造影显示的无症状DVT；超声或静脉造影证实的有症状DVT；有症状、经客观证实的肺栓塞；以及出血。所有指标均由当地和中央研究实验室的盲法判定进行评估。
经中央判定，希美加群组静脉血栓栓塞发生率为19.2%（276例患者中的53例），华法林组为25.7%（261例患者中的67例）（差异为-6.5个百分点[95%CI，-13.5至0.6个百分点]；P = 0.070）。经局部评估，希美加群组发生率为25.4%，华法林组为33.5%（P = 0.043）。希美加群组和华法林组分别有1.7%和0.9%的患者发生大出血，7.8%和6.4%的患者发生小出血。两组间与出血相关的变量无显著差异。
对于静脉血栓栓塞的预防，全膝关节置换术后次日早晨开始使用固定剂量的希美加群耐受性良好，且至少与华法林一样有效，但无需凝血监测或剂量调整。
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