Latest advances in the reversal strategies for direct oral anticoagulants

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology Pub Date : 2024-02-13 DOI:10.1111/fcp.12992

Jean Escal, Julien Lanoiselée, Géraldine Poenou, Paul Zufferey, Silvy Laporte, Patrick Mismetti, Xavier Delavenne

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引用次数: 0

Abstract

Background

Since the late 2000s, Europe has granted approval for various thrombotic risk-related uses of direct oral anticoagulants (DOACs). Unlike traditional anticoagulants, DOACs do not necessitate routine coagulation monitoring. Nevertheless, clinical practice often encounters bleeding events associated with these medications, making the need for effective reversal strategies evident.

Objectives

The study aims to take stock of current reversal strategies for DOACs, with a particular emphasis on the latest compounds that have been developed or are currently under development.

Methods

For obtaining information regarding the ongoing reversal strategies and the compounds under development, we referred to ClinicalTrials website, PubMed, and Google Scholar.

Results

In 2024, two specific antidotes to DOACs have already received approval when reversal of anticoagulation is needed owing to life-threatening or uncontrolled bleeding: idarucizumab that reverses the effects of dabigatran, and andexanet alfa, designed to counteract activated factor X inhibitors such as apixaban and rivaroxaban. Furthermore, ciraparantag, a potential universal reversal agent, is currently in advanced stages of clinical development. Concerns remain regarding the safety of specific reversal agents, especially concerning the risk of thrombosis. Additionally, the cost of these antidotes remains high. Consequently, nonspecific strategies to counteract anticoagulant medications, including activated charcoal, hemodialysis, and concentrates of coagulation factors, still have utility.

Conclusion

With the validation of specific and nonspecific antidotes, DOACs could supplant traditional oral anticoagulants. This progress represents a significant advancement in anticoagulation therapy. However, ongoing research is crucial to address remaining safety concerns of the specific reversion agents of DOACs in clinical practice.

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直接口服抗凝剂逆转策略的最新进展。

背景：自 2000 年代末以来，欧洲已批准直接口服抗凝剂（DOACs）的各种血栓风险相关用途。与传统抗凝药不同，DOACs 无需进行常规凝血监测。然而，临床实践中经常会遇到与这些药物相关的出血事件，因此显然需要有效的逆转策略：本研究旨在对目前 DOACs 的逆转策略进行评估，尤其侧重于已经开发或正在开发的最新化合物：方法：我们参考了 ClinicalTrials 网站、PubMed 和 Google Scholar，以获取有关当前逆转策略和正在开发的化合物的信息：结果：2024 年，有两种针对 DOAC 的特效解毒剂已获得批准，用于因危及生命或出血无法控制而需要逆转抗凝时的治疗：可逆转达比加群作用的 idarucizumab 和旨在对抗阿哌沙班和利伐沙班等活化因子 X 抑制剂的 andexanet alfa。此外，一种潜在的通用逆转剂 ciraparantag 目前正处于临床开发的后期阶段。对于特定逆转剂的安全性，尤其是血栓形成的风险，仍存在担忧。此外，这些解毒剂的成本仍然很高。因此，包括活性炭、血液透析和凝血因子浓缩物在内的非特异性抗凝药物解毒策略仍有用武之地：结论：随着特异性和非特异性解毒剂的验证，DOAC 可取代传统的口服抗凝剂。这一进展标志着抗凝疗法的重大进步。然而，要解决 DOACs 特异性逆转剂在临床实践中仍然存在的安全问题，持续的研究至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fundamental & Clinical Pharmacology 医学-药学

CiteScore

5.30

自引率

6.90%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.