The Real Decoy

Abstract

Although new oral anticoagulants are replacing warfarin for stroke prevention in atrial fibrillation and for the prevention and treatment of venous thromboembolism, the lack of antidotes is a concern. Consequently, the development of a potential antidote for oral factor Xa inhibitors, such as rivaroxaban and apixaban, represents a major breakthrough. For decades, vitamin K antagonists (VKAs), such as warfarin, were the only orally available anticoagulants. This situation changed with the recent introduction of oral direct thrombin and factor Xa inhibitors. Designed to be given in fixed doses without laboratory monitoring, the new oral anticoagulants (NOACs) are more convenient to administer than warfarin. When compared with warfarin in large phase III clinical trials, NOACs were at least as effective as warfarin, but were associated with less intracranial bleeding. Despite these advantages, however, some clinicians are reluctant to use NOACs because specific antidotes are lacking. In a recent report in Nature Medicine , Lu et al have taken the first step to addressing this unmet medical need. These investigators developed a bioengineered recombinant variant of factor Xa that serves as an antidote for oral and parenteral factor Xa inhibitors. Not only does the antidote reverse the anticoagulant effect of oral factor Xa inhibitors in vitro and in animals, but it also reduces blood loss induced by these agents in rat tail transection and rabbit liver laceration bleeding models. Based on these promising results, the antidote is now undergoing phase II evaluation in humans. If the preclinical findings are confirmed in humans, this antidote has the potential to increase usage of the oral factor Xa inhibitors and streamline their management in situations where rapid reversal is needed in preparation for urgent surgery or intervention, or in patients with serious bleeding. Oral anticoagulants are used for long-term prevention and treatment of venous and arterial …