Lévy Samuel
Aix-Marseille Université, 2 Place Delibes, 13008, Marseille, France,
J Interv Card Electrophysiol. 2014 Sep;40(3):269-75. doi: 10.1007/s10840-014-9910-2. Epub 2014 Jun 18.
New oral anticoagulants (NOACs) have emerged as an alternative therapy to warfarin in the treatment of arterial and venous thromboembolism and in stroke prevention in patients with non-valvular atrial fibrillation (AF). Three of them, i.e., dabigatran, rivaroxaban, and apixaban, have been approved for clinical use in North America and in a number of European countries. In non-valvular AF, their approval was based on large randomized trials showing that they are non-inferior or even, in some instances, superior to warfarin. Dabigatran is a direct thrombin (factor IIa) inhibitor; rivaroxaban and apixaban are direct factor Xa inhibitors. Before using NOACs, it is recommended to become familiar with their pharmacological characteristics and their metabolism. The absence of specific antidotes is often cited as part of the possible weaknesses of NOACs. Antidotes are perceived to be useful in emergency situations such as life-threatening bleeding or non-elective major surgery. NOACs do not require blood monitoring, and therefore, patient compliance to the treatment is essential. For the present time, there are no specific antidotes available for the three NOACs approved for clinical use. However, phase I or phase II research studies in this area are ongoing. For dabigatran, a specific antidote has been tested in a rat model of anticoagulation, and a study in healthy male volunteers has been recently reported. For rivaroxaban, prothrombin complex concentrates (PCCs) have been found to completely reverse the prolongation of the prothrombin time induced by this NOAC. For apixaban, recombinant factor VII was found in an experimental study using human blood to be superior to activated PCC (aPCC) and PCC. More specific antidotes for rivaroxaban and apixaban are in phases I and II evaluation. The management of patients suffering from a major bleeding or requiring a non-elective major surgery includes non-specific reversal agents and is discussed in the light of a recent position paper and of current literature. Most recommendations are based on expert opinions only as randomized trials using agents for reversal of anticoagulation in case of life-threatening bleeding or of major urgent surgery are not available.
新型口服抗凝药（NOACs）已成为华法林在治疗动脉和静脉血栓栓塞以及预防非瓣膜性心房颤动（AF）患者中风方面的替代疗法。其中三种，即达比加群、利伐沙班和阿哌沙班，已在北美和一些欧洲国家获批用于临床。在非瓣膜性AF中，它们的获批是基于大型随机试验，表明它们不劣于甚至在某些情况下优于华法林。达比加群是一种直接凝血酶（因子IIa）抑制剂；利伐沙班和阿哌沙班是直接因子Xa抑制剂。在使用NOACs之前，建议熟悉它们的药理学特性及其代谢情况。缺乏特异性解毒剂常被认为是NOACs可能存在的弱点之一。解毒剂被认为在诸如危及生命的出血或非选择性大手术等紧急情况下有用。NOACs不需要血液监测，因此，患者对治疗的依从性至关重要。目前，对于已获批临床使用的三种NOACs尚无特异性解毒剂。然而，该领域的I期或II期研究正在进行中。对于达比加群，一种特异性解毒剂已在大鼠抗凝模型中进行了测试，最近有一项针对健康男性志愿者的研究报告。对于利伐沙班，已发现凝血酶原复合物浓缩物（PCCs）可完全逆转该NOAC引起的凝血酶原时间延长。对于阿哌沙班，在一项使用人血的实验研究中发现重组因子VII优于活化PCC（aPCC）和PCC。针对利伐沙班和阿哌沙班的更特异性解毒剂正处于I期和II期评估阶段。对大出血患者或需要进行非选择性大手术的患者的管理包括非特异性逆转剂，并根据最近的立场文件和当前文献进行讨论。大多数建议仅基于专家意见，因为尚无在危及生命的出血或重大紧急手术情况下使用抗凝逆转剂的随机试验。
