ESC Congress 2016 - 37

Your FREE access to ESC Congress content all year long www.escardio.org/365 ESC CONGRESS 2016 IN REVIEW Before administration of an antidote such as idarucizumab, it is important to identify the NOAC dose and the time since last administration, perform a renal and liver function test, test for signs of coagulopathy, and use a specific anticoagulation test; as well as follow management protocols for patients with moderate/severe bleeding/ urgent surgery and those having life-threatening bleeding/emergency surgery. Although unresolved questions remain, idarucizumab appears effective for restoring coagulation and it is appropriate for emergency treatment of bleedings without any safety concerns. Sven Wassmann, MD, PhD, ISAR Heart Center, Munich, Germany, focused on the development of andexanet alfa (see also page 29) and ciraparantag (PER977). Andexanet alfa is a recombinant truncated fXa, which acts as a catalytically inactive fXa decoy to prevent the anticoagulant effect of fXa inhibitors. It has no known interaction with other coagulation factors except tissue factor pathway inhibitor (TFPI), nor antibody signal, thus has a different mechanism of action compared with idarucizumab. Andexanet alfa, given as a bolus and a bolus plus infusion to healthy older adults significantly (P < .05) decreased anti-fXa activity of apixaban and rivaroxaban relative to baseline and placebo in the ANNEXA-A and ANNEXA-R studies [Siegal DM et al. N Engl J Med. 2015]. Unbound apixaban and rivaroxaban were significantly Figure 2. High-Dose Idarucizumab More Effective Than Low Dose in Elderly Patients (Aged 65 to 80 Years) Figure 3. High-Dose Idarucizumab More Effective Than Low Dose in Renally Impaired 85 85 80 80 75 75 Diluted Thrombin Time, s Diluted Thrombin Time, s Alexander Niessner, MD, Medical University of Vienna, Vienna, Austria, reviewed the current data concerning idarucizumab, which was approved last year to reverse the anticoagulant effect of dabigatran. It has an immediate onset that lasts 12 to 24 hours and can be readministered after that. Importantly, it does not elicit any immune response. An interim analysis of data from the RE-VERSE AD trial for 90 patients with serious bleeding or who required an urgent procedure, demonstrated that idarucizumab reversed the anticoagulant effects of dabigatran and restored hemostasis within minutes in the vast majority of patients (>90% of patients)[Pollack CV Jr. et al. N Engl J Med. 2015]. Bleeding sites (for those patients not requiring an urgent surgical procedure) included gastrointestinal (39%), intracranial (35%), trauma related (18%), or other (22%). Indications for emergency surgery included bone fractures, acute cholecystitis, or catheter placement due to acute renal insufficiency. Dabigatran can be restarted 24 hours after exposure to idarucizumab, if the patient is clinically stable and adequate hemostasis has been achieved, and patients can be re-exposed to idarucizumab [Glund S et al. J Am Col Cardiol. 2016]. When treating elderly patients and those with renal impairment the 5-g dose is always recommended and the only dose approved by FDA/EMA (Figures 2 and 3) [Glund S et al. Clin Pharmacokinet. 2016]. 70 65 60 55 50 45 70 65 60 55 50 45 40 40 35 35 30 30 25 25 BL -2 0 0.5 1.0 1.5 2.0 4 3 12 16 20 24 BL -2 0 0.5 1.0 1.5 2.0 4 Idarucizumab RI: 60-90, 150 mg DE/ 1 g idarucizumab RI: 60-90, 150 mg DE/ 1 g placebo 3 12 16 20 24 Time Post Idarucizumab, h Time Post Idarucizumab, h Idarucizumab RI: 60-90, 150 mg DE/ 5 g idarucizumab RI: 60-90, 150 mg DE/ 5 g placebo RI: 60-90, 150 mg DE/ 1 g idarucizumab RI: 60-90, 150 mg DE/ 1 g placebo RI: 60-90, 150 mg DE/ 5 g idarucizumab RI: 60-90, 150 mg DE/ 5 g placebo DE, dabigatran etexilate; RI, renal impairment. Reprinted from Glund, S., Stangier, J., van Ryn, J. et al. Effect of Age and Renal Function on Idarucizumab Pharmacokinetics and Idarucizumab-Mediated Reversal of Dabigatran Anticoagulant Activity in a Randomized, Double-Blind, Crossover Phase Ib Study. Clin Pharmacokinet. 2016. doi:10.1007/s40262-016-0417-0. By permission of Springer International Publishing. Official Peer-Reviewed Highlights From ESC Congress 2016 37 http://www.escardio.org/365

Table of Contents for the Digital Edition of ESC Congress 2016