ESC Congress 2016 - 36

sElEcTEd uPdATEs Idarucizumab, Andexanet alfa, and Ciraparantag Open New Era for NOAC Therapy Written by Maria Vinall Official Peer-Reviewed Highlights From With the development of reversal agents, management strategies for patients being treated with non-vitamin K antagonist oral anticoagulants (NOACs) are rapidly changing. Gregory YH Lip, MD, University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom, addressed when and how to use these new agents. Three agents were discussed during this symposium: idarucizumab, andexanet alfa, and ciraparantag. Idarucizumab is a humanized antibody fragment that competitively, specifically, and rapidly binds dabigatran and has no off-target effects. Andexanet alfa is a recombinant protein designed to reverse the anticoagulant effect of direct and indirect factor Xa (fXa) inhibitors. Ciraparantag (PER977) is a small synthetic molecule, developed to target direct thrombin and fXa inhibitors as well as low-molecular-weight heparins. Idarucizumab was approved by the United States FDA and the European Medicines Agency (EMA) in 2015. Andexanet alfa is under review at both agencies while studies are ongoing with ciraparantag. Bleeding is not uncommon among patients treated with NOACs and, although most bleeds are minor or minimal, more serious bleeds such as intracranial and massive gastrointestinal bleeding sometimes require therapy beyond blood support. The 2016 European Society of Cardiology (ESC) guidelines offer specific guidelines for the management of active bleeding in patients with atrial fibrillation (AF) following anticoagulation use (Figure 1) [Kirchhof P et al. Eur Heart J. 2016]. The necessity for reversal should be restricted to cases where there is bleeding with hemodynamic instability, it is not possible to postpone surgery, or if the bleeding is life-threatening due to the bleeding site (eg, intracranial bleeding). These antidotes do work and provide an off switch for NOACs, hence they are a game changer as well as a psychological crutch. Figure 1. 2016 ESC Guidelines for the Management of Active Bleeding in AF Patients Receiving Anticoagulation Patients with active bleeding Compress bleeding sites mechanically Assess hemodynamic status, blood pressure, basiccoagulation parameters, blood count, and kidney function Obtain anticoagulation history (last NOAC/VKA dose) VKA NOAC Delay VKA until INR< 2 Delay NOAC for 1 dose or 1 day Add symptomatic treatment Fluid replacement Blood transfusion Treat bleeding cause Consider adding vitamin K (1-10 mg) Consider PCC and FFP Consider replacement of platelets when appropriate Minor Moderate-severe Add symptomatic treatment Fluid replacement Blood transfusion Treat bleeding cause Consider adding oral charcoal if recently ingested NOAC Severe or life-threatening Consider specific antidote or PCC if antidote unavailable Consider replacement of platelets when appropriate FFP, fresh frozen plasma; NOAC, non-vitamin K antagonist oral anticoagulants; PCC, prothrombin complex concentrate; VKA, vitamin K antagonist. Reprinted from Kirchhof P et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016. doi:10.1093/eurheartj/ehw210. By permission of Oxford University Press on behalf of the European Society of Cardiology. 36 October 2016 medicom-publishers.com/mcr http://www.medicom-publishers.com/mcr

Table of Contents for the Digital Edition of ESC Congress 2016