Reversal of target-specific oral anticoagulants

• Published in: Drug discovery today Vol. 19; no. 9; pp. 1465 - 1470
• Main Authors: Siegal, Deborah M., Cuker, Adam
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2014
• Subjects: Administration, Oral; Animals; Anticoagulants - adverse effects; Anticoagulants - pharmacology; Antidotes - adverse effects; Antidotes - pharmacology; Antithrombins - adverse effects; Antithrombins - pharmacology; Disease Models, Animal; Factor Xa Inhibitors - adverse effects; Factor Xa Inhibitors - pharmacology; Hemorrhage - chemically induced; Hemorrhage - drug therapy; Humans
• ISSN: 1359-6446; 1878-5832; 1878-5832
• DOI: 10.1016/j.drudis.2014.05.013

•No antidotes are currently available for reversal of the target-specific oral anticoagulants (TSOACs).•Nonspecific and specific agents have been put forward as potential reversal strategies.•Evidence for the efficacy and safety of these strategies is of low quality.•The evidence is derived from in vitro investigations, animal bleeding models and human volunteer studies.•Studies of patients with TSOAC-associated bleeding that use clinically relevant outcomes are urgently needed. Target-specific oral anticoagulants (TSOACs) provide safe and effective anticoagulation for the prevention and treatment of thrombosis in a variety of clinical settings by interfering with the activity of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban, betrixaban). Although TSOACs have practical advantages over vitamin K antagonists (VKAs), there are currently no antidotes to reverse their anticoagulant effect. Herein we summarize the available evidence for TSOAC reversal using nonspecific and specific reversal agents. We discuss important limitations of existing evidence, which is derived from studies in human volunteers, animal models and in vitro experiments. Studies evaluating the safety and efficacy of reversal agents on clinical outcomes such as bleeding and mortality in patients with TSOAC-associated bleeding are needed.