The newest study regarding the reversal of the novel oral anticoagulants also concerns the newest of their family – edoxaban, joining a market already occupied by rivaroxaban and apixiban. Yes, it’s just another “me too” drug trying to shoehorn its way into the massive warfarin-replacement market – but, at least, this is useful evidence.
4-Factor prothrombin concentrate complexes have been established as a treatment option in the setting of hemorrhagic complications during anticoagulation with the Factor Xa inhibitors. However, the initial studies of PCCs primarily concerned themselves with laboratory markers of reversal, and any live bleeding studies were in animals (rabbits!). For this study, however, the authors & Daiichi Sankyo paid 110 healthy volunteers to take edoxaban, then undergo punch biopsy, and then receive either placebo or 4-factor PCC in either 10 IU/kg, 25 IU/kg, or 50 IU/kg doses.
And, pleasantly, it works – in a dose dependent fashion, even, with 50 IU/kg providing the most effective reversal. So, this essentially confirms what we thought we knew about PCCs based on surrogate markers and animal studies. These volunteers only suffered a minor dermatologic procedure – and are not critically ill patients with other associated coagulopathies – but it still provides reasonable insight.
How this reversal strategy will fit versus andexanet alfa, a NOAC-specific reversal agent, remains to be seen – particularly with regards to cost and pro-thrombotic adverse effects.
“Edoxaban Effects on Bleeding Following Punch Biopsy and Reversal by a 4-Factor Prothrombin Complex Concentrate”
http://circ.ahajournals.org/content/early/2014/11/16/CIRCULATIONAHA.114.013445.abstract