The absence of an antidote may soon disappear as a reason to avoid prescribing a novel oral anticoagulant to patients with atrial fibrillation, based on promising phase III trial results.
The Food and Drug Administration has just approved a fourth NOAC, edoxaban (SAVAYSA, another factor Xa inhibitor) for the treatment of non-valvular atrial fibrillation. Approval was based on the results of the ENGAGE-TIMI 48 trial which showed that edoxaban at a dose of 60 mg daily (and 30 mg for those with renal impairment) was non-inferior to warfarin and associated with less bleeding. FDA did issue a black box warning for those with creatinine clearance >95 mL/min, in whom the drug was associated with more strokes compared with warfarin, likely due to increased clearance of the drug. More information, here.
The phase 3 study ANNEXA-A (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXA Inhibitors â Apixaban), showed rapid and near complete reversal (â94%) of the anticoagulant effects of apixaban in healthy volunteers without any serious adverse side effects. The results of this trial were presented at the American Heart Association Scientific Sessions 2014. More information, here.
Preliminary data from ANNEXA-R study (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXA Inhibitors â Rivaroxaban), which will be presented at the American College of Cardiology Scientific Sessions 2015, showed that 800 mg of intravenous andexanet alfa was effective in near complete reversal of the steady-state effects of rivaroxaban.More information, here.
The very good news in the world of atrial fibrillation is the recent announcement of phase 3 trial results that showed andexanet alfa provided rapid and near complete reversal (â94%) of the factor Xa inhibitor apixaban. A similiar trial with rivaroxaban is under way as is a trial to gain FDA approval for the direct thrombin inhibitor antidote idarucizumab. Absence of a reliable reversal agent is believed to be an impediment to wider acceptance of the novel oral anticoagulants NOAC). In other AF news, the FDA has just approved edoxaban, the fourth NOAC available in the United States.