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Reversing factor Xa inhibitors – clinical utility of andexanet alfa

Authors Kaatz S, Bhansali H, Gibbs J, Lavender R, Mahan CE, Paje DG

Received 13 June 2017

Accepted for publication 11 July 2017

Published 13 September 2017 Volume 2017:8 Pages 141—149

DOI https://doi.org/10.2147/JBM.S121550

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Martin Bluth

Scott Kaatz,1 Hardik Bhansali,1 Joseph Gibbs,2 Robert Lavender,3 Charles E Mahan,4 David G Paje5

1Division of Hospital Medicine, 2Department of Internal Medicine, Henry Ford Hospital, Detroit, MI, 3Division of General Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 4University of New Mexico, Presbyterian Healthcare Services, Albuquerque, NM, 5Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA

Abstract: Approximately half of patients started on an oral anticoagulant in the USA now receive one of the newer direct oral anticoagulants (DOACs). Although there is an approved reversal agent for the direct thrombin inhibitor dabigatran, a specific reversal agent for the anti-factor Xa (FXa) DOACs has yet to be licensed. Unlike the strategy to reverse the only oral direct thrombin inhibitor with idarucizumab, which is a humanized monoclonal antibody fragment, a different approach is necessary to design a single agent that can reverse multiple anti-FXa medications. Andexanet alfa is a FXa decoy designed to reverse all anticoagulants that act through this part of the coagulation cascade including anti-FXa DOACs, such as apixaban, edoxaban and rivaroxaban, and indirect FXa inhibitors such as low-molecular-weight heparins. This narrative reviews the development of andexanet alfa and explores its basic science, pharmacokinetics/pharmacodynamics, animal models, and human studies.

Keywords: factor Xa, DOAC, andexanet alfa, reversal, rivaroxaban, apixaban

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