#Apixaban antidote trial

The ANNEXA-4 is the ongoing safety study. Andexanet has not been studied in patients with disseminated intravascular coagulation within the previous 2 weeks or in those who receive prothrombin complex concentrate, recombinant factor VIIa, or blood products within 7 days of bleeding event. To reduce the incidence of such events, it is suggested that anticoagulation be resumed as soon as possible. There are several warnings associated with andexanet use, including arterial and venous thromboembolic events, ischemic events such as MI and stroke, or cardiac arrest/sudden death (occurred in ~18% of patients in the ANNEXA-4 safety study with a median time to event of 6 days). There have been no studies yet of edoxaban and andexanet. A bolus of this agent results in a rapid and sustained decrease in levels of anti-FXa (>90% for rivaroxaban >93% for apixaban in ~50% of patients).

#Apixaban antidote trial

The approval came via FDAвЂ™s accelerated approval pathway and is based on reversal of rivaroxaban in the ANNEXA-R trial and of apixaban in the ANNEXA-A trial in healthy volunteers.

The scenario changed in early May 2018 with the FDA approval of andexanet alfa (Andexxa, Portola Pharmaceuticals), for the reversal of apixaban and rivaroxaban in situations of life-threatening or uncontrolled bleeding. The lack of a reversal agent for the FXa inhibitors often leads patients to question the safety of these medications. Fresh frozen plasma is typically used to reverse warfarin in acute, life-threatening situations similarly, idarucizumab (Praxbind) was approved by the FDA in 2015 to reverse the action of the direct thrombin inhibitor dabigatran (Pradaxa). Until now, one of the main limitations to clinical use of three of the DOACs-the factor Xa (FXa) inhibitors apixaban, rivaroxaban, and edoxaban, was the lack of a reversal agent. Whenever I have a conversation with a patient about starting anticoagulation for nonvalvular atrial fibrillation (AF) with a CHA 2DS 2-Vasc score в‰Ґ2, I always go into the advantages and disadvantages of warfarin vs the direct oral anticoagulants (DOACs).