Research Center on Thromboembolic Diseases and Antithrombotic Drugs, Department of Medicine and Surgery, University of Insubria, Varese, Italy.
Research Center on Thromboembolic Diseases and Antithrombotic Drugs, Department of Medicine and Surgery, University of Insubria, Varese, Italy.
Thromb Res. 2018 Apr;164 Suppl 1:S119-S123. doi: 10.1016/j.thromres.2018.01.006.
The direct oral anticoagulants (DOACs) are recommended as the first-choice anticoagulants for both stroke prevention in patients with non-valvular atrial fibrillation and the treatment and secondary prevention of venous thromboembolism. DOACs cause bleeding, albeit less than warfarin. Most bleeding complications can be controlled by general reversal strategies and supportive care. However, in case of life-threatening bleeding, or when urgent invasive procedures are needed, a more rapid and thorough reversal may be required. Idarucizumab, andexanet alfa and ciraparantag have been developed as reversal agents for the DOACs. To date idarucizumab is the only approved antidote and is specific for dabigatran. Andexanet alfa, a reversal agent for the factor Xa inhibitors, is still under investigation, but its approval by regulatory agencies is expected soon. Ciraparantag, a universal antidote, is in an earlier stage of development. Based on the results of clinical trials to date, these compounds appear to be breakthrough for urgent and emergency reversal. When administered at fixed doses, they ensured a rapid, efficient and safe restoration of haemostasis. From a practical perspective, all hospitals should develop local protocols to ensure safe and efficient clinical implementation of reversal strategies. Post-marketing studies will be essential to assess the evolution of management strategies and to confirm the safety and effectiveness of these agents.
直接口服抗凝剂(DOACs)被推荐为非瓣膜性心房颤动患者预防中风和治疗及二级预防静脉血栓栓塞的首选抗凝剂。DOACs 会导致出血,尽管比华法林少。大多数出血并发症可以通过一般逆转策略和支持性护理来控制。然而,在危及生命的出血情况下,或需要紧急侵入性手术时,可能需要更快速和彻底的逆转。Idarucizumab、andexanet alfa 和 ciraparantag 已被开发为 DOACs 的逆转剂。迄今为止,idarucizumab 是唯一获得批准的解毒剂,专门针对达比加群。针对 Xa 因子抑制剂的逆转剂 andexanet alfa 仍在研究中,但预计很快会获得监管机构的批准。作为通用解毒剂的 ciraparantag 处于早期开发阶段。根据迄今为止的临床试验结果,这些化合物似乎是紧急和急诊逆转的突破。以固定剂量给药时,它们可确保快速、高效和安全地恢复止血。从实际角度来看,所有医院都应制定本地方案,以确保安全、有效地实施逆转策略。上市后研究对于评估管理策略的演变以及确认这些药物的安全性和有效性至关重要。