When and how to use antidotes for the reversal of direct oral anticoagulants: guidance from the SSC of the ISTH


The direct oral anticoagulants (DOACs), which include dabigatran, rivaroxaban, apixaban, and edoxaban, are licensed for stroke prevention in patients with atrial fibrillation and for prevention and treatment of venous thromboembolism [1]. As a class, the DOACs are at least as effective as vitamin K antagonists (VKAs) but are associated with less life-threatening bleeding, particularly intracranial hemorrhage [2]. Although all anticoagulants can produce bleeding, the outcomes of major bleeds with DOACs are no worse than those with VKAs even in the absence of clinically available antidotes [3]. Nonetheless, antidotes for the DOACs would be useful as one component of strategies for management of serious bleeding, or for rapid reversal of the DOACs before urgent interventions.

Three antidotes for the DOACs are under various stages of development. Idarucizumab (Praxbind®), the antidote for dabigatran, is now licensed in the United States and Europe. Andexanet alfa, the antidote for the oral factor Xa (FXa) inhibitors, is undergoing phase III investigation [4]. Ciraparantag (PER977), an agent reported to reverse the anticoagulant effects of all of the DOACs, is at an earlier stage of development. Although each of these agents reverses the anticoagulant effects of the DOACs through different mechanisms and some are more specific than others, for simplicity, we will refer to all of them as antidotes. This report (i) describes the mechanism of action of the antidotes, (ii) reviews the available clinical data, and (iii) provides guidance on potential indications for their use.

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Levy JH, Ageno W, Chan NC, et al. J Thromb Haemost 2016;14:623–7.