Prescrire Int. 2005 Aug;14(78):127-32.
(1) The reference drug for prophylaxis against venous thromboembolism after hip or knee replacement surgery is a low-molecular-weight heparin (LMWH), given subcutaneously for 1 to 5 weeks. Vitamin K antagonists, including warfarin, have similar risk-benefit balances. (2) Subcutaneous melagatran and its oral metabolic precursor ximelagatran have recently been granted marketing authorisation in France for use as prophylaxis after hip or knee replacement surgery. Melagatran, unlike LMWH, is a specific thrombin inhibitor. (3) There are four randomised double-blind trials in more than 9000 patients comparing these agents with a LMWH (enoxaparin in three trials, dalteparin in one). Melagatran was given subcutaneously for one or two days before being replaced with ximelagatran (as soon as oral feeding was possible) for 6 to 9 days. These trials showed no advantage of melagatran-ximelagatran in terms of clinical endpoints such as symptomatic deep venous thrombosis, pulmonary embolism, and death from all causes. (4) Three randomised double-blind trials have compared ximelagatran with warfarin in more than 5000 patients. Treatment lasted 7 to 12 days. Ximelagatran was no better than warfarin when assessed using clinical endpoints. (5) In these trials melagatran-ximelagatran did not increase the risk of bleeding compared with LMWH or warfarin. (6) Melagatran-ximelagatran can cause an increase in serum transaminase activity, and is contraindicated if pretreatment serum transaminase activity is more than twice the upper limit of normal. (7) Trials versus warfarin showed a higher risk of myocardial infarction in patients taking ximelagatran (0.7% versus 0.16%). (8) There are few data on the patient subgroups most likely to receive melagatran-ximelagatran, namely patients over 75, underweight and overweight patients, and patients with renal failure. (9) There is currently no clotting test that allows the melagatran-ximelagatran dose regimen to be adjusted in patients who have an increased risk of adverse effects due to overdosing. There is no available antidote if overdose occurs. (10) Erythromycin increases melagatran bioavailability, thereby increasing the bleeding risk. Melagatran and ximelagatran must not be combined with other anticoagulants, thrombolytic agents or antiplatelet drugs because of a increased bleeding risk. (11) In practice, low-molecular-weight heparin remains the reference prophylactic treatment for venous thromboembolism after hip or knee replacement surgery.
(1) 髋或膝关节置换术后预防静脉血栓栓塞的参考药物是低分子量肝素（LMWH），皮下注射1至5周。包括华法林在内的维生素K拮抗剂具有相似的风险效益平衡。(2) 皮下注射的美拉加群及其口服代谢前体希美加群最近在法国已获得上市许可，用于髋或膝关节置换术后的预防。与LMWH不同，美拉加群是一种特异性凝血酶抑制剂。(3) 有四项针对9000多名患者的随机双盲试验，将这些药物与LMWH（三项试验用依诺肝素，一项试验用达肝素）进行比较。美拉加群在皮下注射1或2天后，改为希美加群（一旦可以口服喂养），持续6至9天。这些试验表明，在有症状的深静脉血栓形成、肺栓塞和全因死亡等临床终点方面，美拉加群 - 希美加群并无优势。(4) 三项随机双盲试验在5000多名患者中比较了希美加群和华法林。治疗持续7至12天。使用临床终点评估时，希美加群并不比华法林更好。(5) 在这些试验中，与LMWH或华法林相比，美拉加群 - 希美加群并未增加出血风险。(6) 美拉加群 - 希美加群可导致血清转氨酶活性升高，若治疗前血清转氨酶活性超过正常上限两倍则禁用。(7) 与华法林的试验显示，服用希美加群的患者发生心肌梗死的风险更高（0.7% 对0.16%）。(8) 关于最可能接受美拉加群 - 希美加群治疗的患者亚组的数据很少，即75岁以上患者、体重过轻和超重患者以及肾衰竭患者。(9) 目前没有凝血试验可用于调整美拉加群 - 希美加群剂量方案，以适用于因用药过量而出现不良反应风险增加的患者。若发生过量用药，没有可用的解毒剂。(10) 红霉素会增加美拉加群的生物利用度，从而增加出血风险。由于出血风险增加，美拉加群和希美加群不得与其他抗凝剂、溶栓剂或抗血小板药物联合使用。(11) 在实际应用中，低分子量肝素仍然是髋或膝关节置换术后静脉血栓栓塞的参考预防性治疗药物。
