Medical Director, NP Cardiology Fellowship Medical Director, Anticoagulation Clinic Assistant Professor of Medicine Vascular Medicine, Division of Cardiovascular Diseases Scottsdale, USA
The clinical use of DOACs become more widespread, multiple drug companies initiated development of agents that have the potential complete and specific reversal of DOACs.
Idarucizumab (Praxbind®, Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT USA) idarucizumab is a humanized monoclonal antibody Fab fragment directed against dabigatran, with an affinity towards dabigatran of approximately 350 times that of thrombin. There was normalization of aPTT and TT after infusion and improved reversal of anticoagulant effect vs PCC and aPCC as measured by fibrin deposition. Praxbind® (idarucizumab) as a once off 5g IV bolus dose is approved for clinical use in patients on dabigatran, in cases of emergency surgery or urgent procedures and in life-threatening or uncontrolled bleeding.
Andexanet alfa (Annexa®, Portola Pharmaceuticals, Inc., San Francisco CA USA).
Designed as a recombinant fXa decoy protein, andexanet alfa retains high affinity for fXa inhibitors but due to the lack of the γ-carboxyglutamic acid terminal required for fXa activity. The phase II RCTs using edoxaban, rivaroxaban and apixaban demonstrated reversal of all agents measured with excellent tolerability if a bolus followed by continuous infusion was used. It is not yet clear whether there are agent specific dosing requirements for reversibility. Currently two phase III RCTs are ongoing, designated as ANNEXA-R (with rivaroxaban) and ANNEXA-A (with apixaban), with some preliminary results having being recently presented.
Aripazine (PER977, Perosphere Inc., Danbury, CT USA).
This synthetic water soluble negatively charge small molecule reversal agent that selectively reverses a whole range of anticoagulants that have vastly different chemical structures and targets.