Direct oral anticoagulants: Current indications and unmet needs in the treatment of venous thromboembolism
Direct oral anticoagulants: Current indications and unmet needs in the treatment of venous thromboembolism
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DOI：
10.1016/j.phrs.2016.06.023
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发表时间：
2017-04-01
影响因子：
9.3
通讯作者：
Laporte, Silvy
中科院分区：
文献类型：
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作者：
Bertoletti, Laurent;Ollier, Edouard;Laporte, Silvy
随着直接口服抗凝剂（DOAC）的发展，急性静脉血栓栓塞（VTE）的治疗正在完全改变。利伐沙班、阿哌沙班和依度沙班直接抑制因子Xa，而达比加群抑制因子IIa。所有这些药物均建议口服，并且具有药理学相似性：固定剂量，无任何治疗药物监测，转运蛋白P-糖蛋白对所有药物的关键作用，以及CYP 3A 4介导的抗Xa代谢，半衰期短，肾脏消除速率可变。超过25000例急性VTE患者被纳入III期研究。利伐沙班和阿哌沙班挑战了所有常规治疗（肠外肝素，然后是抗维生素K拮抗剂），而依度沙班和达比加群仅挑战抗维生素K拮抗剂。所有DOAC均符合非劣效性疗效终点（治疗期间复发性VTE），而达比加群的大非劣效性界值存在争议。然而，它们与更好的安全性和降低大出血风险相关。根据间接比较，DOAC之间在疗效方面没有统计学显著差异，但在安全性方面不排除一些差异。尽管DOAC可以简化大多数急性VTE患者的治疗，但在老年患者、轻度至重度肾损害患者和一些临床亚组（如癌症或慢性血栓栓塞性肺动脉高压）中，其风险/获益比受到质疑。预计对大出血、药物过量或需要手术的患者采用经验证的逆转策略（可能基于实验室监测）。(C)2016爱思唯尔有限公司版权所有。
The treatment of acute venous thromboembolism (VTE) is being completely modified with the development of direct oral anticoagulants (DOACs). Rivaroxaban, apixaban and edoxaban directly inhibit factor Xa, whereas dabigatran inhibits factor Ila. All these drugs are proposed orally, and share pharmacological similarities: fixed doses without any therapeutic drug monitoring, key role of the transporter proteins P-glycoprotein for all of them and metabolism mediated by CYP3A4 for the anti-Xa, short half-life with variable rate of renal elimination. More than 25 000 patients with acute VTE were included in phase -III studies. Rivaroxaban and apixaban challenged all the conventional therapy (parenteral heparins followed by anti-vitamin K antagonists) whereas edoxaban and dabigatran challenged only anti-vitamin K antagonists. All the DOACs met the non-inferiority efficacy endpoint (recurrent VTE during treatment), whereas the large non-inferiority margin was debated for dabigatran. However, they were associated with better safety and a decreased risk of major bleeding. According to indirect comparisons, there were no statistically significant differences between DOACs in terms of efficacy but some differences are not excluded in term of safety. Although DOACs allow for simplification of treatment in the majority of patients with acute VTE, their risk/benefit ratio is questioned in elderly patients, patients with mild-to-severe renal impairment, and in some clinical subgroups such as cancer or chronic thromboembolic pulmonary hypertension. Validated reversal strategies (potentially based on laboratory monitoring) are expected for patients with major bleeding, overdose or with a need for surgery. (C) 2016 Elsevier Ltd. All rights reserved.