By Timofey Sovershaev, PhD student at TREC
Thrombotic complications are a serious risk in several disorders, including atrial fibrillation, venous thromboembolism and many others. Traditionally, vitamin K antagonists (warfarin) or low-molecular weight heparins were used to prevent such complications. During the last years, a novel drug class, factor Xa inhibitors, has been incorporated into clinical practice, as these drugs have the potential to be safer and easier to use than the traditional vitamin K inhibitors. However, until recently, there was no agent to reverse their effects.
In a study published in New England Journal of Medicine, a group of researchers from USA present the results of randomized trial of a potential antidote, Andexanet Alfa. This drug is able to rapidly and completely reverse the action of apixaban (Xarelto) and rivaroxaban (Eliquis).
The study was performed on a group of older healthy volunteers, which corresponds to the population where factor Xa inhibitors are most likely to be used. In total, 101 participants were randomized to receive Andexanet Alfa or placebo in order to study the effects of the drug on the coagulation as well as possible side effects.
Andexanet was shown to be effective in rapidly reversing the action of both apixaban and rivaroxaban. The reversal of anticoagulation was rapid and corresponded with the short half-live of the drug (1 hour) with no serious side effects observed both during the infusion or a prolonged follow-up period.
The authors conclude that in the given population Andexanet Alfa is effective in reversing the action of factor Xa inhibitors and safe to use. The strengths of the study is that it was performed in a population more alike the target population than the previous studies. However, the authors also note that the results are obtained in a healthy population, which is different from the actual target group.
Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL, et al. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N Engl J Med. 2015;373:2413-24.