Koscielny J, Kiesewetter H, Jörg I, Harenberg J
Institute for Transfusion Medicine, Charité Humboldt University, Campus Charité Mitte, Berlin, Germany.
Clin Appl Thromb Hemost. 2007 Jul;13(3):299-307. doi: 10.1177/1076029607302561.
The treatment of acute venous thromboembolism and prophylaxis of recurrent events with heparin/low molecular weight heparin followed by vitamin K antagonists is limited by several factors. Oral direct thrombin inhibitors (ODTIs) showed a better pharmacological activity and might be an alternative in the treatment of venous thromboembolism. The Thrombin Inhibition in Venous Thromboembolism (THRIVE) program performed some studies developing the ODTI ximelagatran for this indication, and it is presented in the overview. The aim of the THRIVE I study was the dose finding, and that of the THRIVE IV study the applicability in hemodynamic stabile pulmonary embolism. A prospective, randomized, double blind trial was performed to compare oral ximelagatran with enoxaparin/warfarin for a 6-month treatment of acute venous thrombosis (THRIVE II and V). A second double blind study compared ximelagatran with placebo over 18 months after a 6-month anticoagulant therapy of acute deep vein thrombosis. The efficacy and safety of treatment of patients with acute deep venous thrombosis who received 2 infinity 36 mg ximelagatran was not inferior to that of patients who received a conventional anticoagulant for prophylaxis of recurrent events over 6 months. Ximelagatran 2 infinity 24 mg significantly reduced recurrent thromboembolic events compared to placebo without increasing the risk for hemorrhage. A reversible symptomless increase of alanine aminotransferase occurs in 6% to 9.6% of patients between months 2 and 4. The results of the follow-up studies suggest that thromboembolic events may recur in patients with acute venous thromboembolism after termination of treatment with both vitamin K antagonists and ximelagatran.
肝素/低分子量肝素随后使用维生素K拮抗剂治疗急性静脉血栓栓塞及预防复发事件受到多种因素的限制。口服直接凝血酶抑制剂（ODTIs）显示出更好的药理活性，可能是治疗静脉血栓栓塞的一种替代方法。静脉血栓栓塞中的凝血酶抑制（THRIVE）项目开展了一些研究来开发用于该适应症的ODTI希美加群，并在综述中进行了介绍。THRIVE I研究的目的是确定剂量，THRIVE IV研究的目的是评估在血流动力学稳定的肺栓塞中的适用性。进行了一项前瞻性、随机、双盲试验，比较口服希美加群与依诺肝素/华法林治疗急性静脉血栓形成6个月的效果（THRIVE II和V）。另一项双盲研究比较了急性深静脉血栓形成6个月抗凝治疗后18个月内希美加群与安慰剂的效果。接受2次每日36毫克希美加群治疗的急性深静脉血栓形成患者预防复发事件6个月的疗效和安全性不低于接受传统抗凝治疗的患者。与安慰剂相比，2次每日24毫克希美加群显著降低了复发血栓栓塞事件，且未增加出血风险。在第2至4个月期间，6%至9.6%的患者出现可逆性无症状丙氨酸转氨酶升高。随访研究结果表明，维生素K拮抗剂和希美加群治疗终止后，急性静脉血栓栓塞患者可能会复发血栓栓塞事件。
