In close timing with the FDA’s approval of edoxaban for reducing the risk of stroke in patients with atrial fibrillation, researchers reported that an agent reversed edoxaban’s anticoagulant effect in a phase 1 study.
Edoxaban (Savaysa, Daiichi Sanko) is a factor Xa inhibitor that was approved by the FDA on Jan. 8, adding the novel oral anticoagulant to a growing list of alternatives to warfarin for patients with nonvalvular atrial fibrillation. The drugs also reduce the risk of venous thromboembolism. But unlike warfarin, their anticoagulation cannot be easily reversed, which poses a problem if patients need emergency surgery or experience serious bleeding.
Senior writer Elliott M. Antmann, MD, of Brigham and Women’s Hospital in Boston, and colleagues published results for a phase 1 trial that tested the use of a four-factor prothrombin complex concentrates (4F PCC) in healthy adults in a two part study. The second part used a blinded and randomized design in 93 volunteers to determine the reversal effect with descending doses of 4F-PCC.
The highest dose in the study was 50 IU/kg, which previously had been shown in healthy volunteers to reverse the effect of two other factor Xa inhibitors, rivaroxaban (Xarelto, Bayer/Johnson & Johnson) and apixaban (Eliquis, Bristol-Myers Squibb). An antidote for dabigatran (Pradaxa, Boehringer Ingelheim), which is a direct thrombin inhibitor, also has been shown to be effective in a trial with healthy people.
At 50 IU/kg, the 4F-PCC completely reversed the effect of a 60 mg dose of edoxaban on bleeding duration. A 25 IU/kg dose achieved partial reversal and a 10 IU/kg dose showed no reversal. The highest dose also completely reversed the effects of edoxaban on endogenous thrombin potential and partially reversed the prothrombin time.
One person in the second part of the study discontinued because of an adverse event and five others dropped out for other reasons. The researchers reported no deaths, serious adverse events or thrombolytic events.
The study, published in the Jan. 6 issue of Circulation, and was funded by Daiichi Sanko.