Specific reversal agents for novel oral anticoagulants, including idarucizumab, andexanet, and PER977, are currently in premarketing studies to address the lack of targeted antidotes.
What are the available and emerging strategies to reverse the anticoagulant effect of novel oral anticoagulants?
While non-specific agents show some efficacy, novel specific antidotes like idarucizumab and andexanet are in development to provide safer and more effective emergency reversal of novel oral anticoagulants.
The direct thrombin inhibitor dabigatran and the anti-Xa agents rivaroxaban, edoxaban, and apixaban are a new generation of oral anticoagulants. Their advantage over the vitamin K antagonists is the lack of the need for monitoring and dose adjustment. Their main disadvantage is currently the absence of a specific reversal agent. Dabigatran's, unlike the anti-Xa agents, absorption can be reduced by activated charcoal if administered shortly after ingestion and it can be removed from the blood with hemodialysis. Prothrombin complex concentrate, activated prothrombin complex concentrate, and recombinant factor VIIa all show some activity in reversing the anticoagulant effect of these drugs but this is based on ex vivo, animal, and volunteer studies. It is unclear, which, if any, of these drugs is the most suitable for emergency reversal. Three novel molecules (idarucizumab, andexanet, and PER977) may provide the most effective and safest way of reversal. These agents are currently in premarketing studies.
Crowther et al. (Fri,) conducted a review in Anticoagulation reversal. Antidotes for novel oral anticoagulants was evaluated. Specific reversal agents for novel oral anticoagulants, including idarucizumab, andexanet, and PER977, are currently in premarketing studies to address the lack of targeted antidotes.