ESC Congress 2016 - 29

Your FREE access to ESC Congress content all year long www.escardio.org/365 ESC CONGRESS 2016 IN REVIEW Figure 1. Primary Efficacy Outcome in ENSURE-AF 2.0 Edoxaban Enoxaparin + Warfarin (mean TTR = 70.8%) 1.5 MI, and CV Death, % Composite of Stroke, SEE, OR (95% CI): 0.50 (0.08-2.36) OR (95% CI): 0.46 (0.12-1.43) OR (95% CI): 1.2% 0.40 (0.04-2.47) 1.0% 1.0 0.8% 0.6% 0.5% 0.5 0.3% 5/1095 0.0 11/1104 Total by Treatment 2/589 TEE Stratum 5/599 3/506 6/510 Non-TEE Stratum CV, cardiovascular; MI, myocardial infarction; SEE, systemic embolic event; TEE, transthoracic echocardiography TTR, time in therapeutic range. a Composite of stroke, SEE, MI, and CV mortality assessed in the ITT population during overall period. Reproduced with permission from A Goette, MD. The primary safety outcome of major and clinically relevant nonmajor bleeding at 31 days post cardioversion showed there were 16 events in the edoxaban arm and 11 events in the enoxaparin/VKA arm, for an event rate of 1.5% vs 1.0% (OR, 1.48; 95% CI, 0.64 to 3.55). Major bleeding was infrequent, with 3 events and 5 events (0.3% vs 0.5%) in the edoxaban and comparator arms, respectively (OR, 0.61; 95% CI, 0.09 to 3.13). Rates of any bleeding event were similar (3.0% vs 3.2%; OR, 0.93; 95% CI, 0.55 to 1.55). The secondary outcome of net clinical benefit, a composite of stroke, systemic embolic event, cardiovascular mortality, and major bleeding, also showed a trend towards a better outcome with edoxaban (8 events vs 16 events with enoxaparin/VKA; 0.7% vs 1.4% event rate; OR, 0.50; 95% CI, 0.19 to 1.25). Renal function did not affect outcomes. Edoxaban appears to be an effective and safe alternative to enoxaparin/VKA for patients with AF undergoing electrical cardioversion and may allow for prompt cardioversion following the start of oral anticoagulation. Andexanet alfa Reverses Factor Xa activity in Patients With Acute Major Bleeding in ANNEXA-4 Trial Written by Phil Vinall Stuart J. Connolly, MD, Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada, reported that in the ANNEXA-4 trial [Connolly SJ et al. N Engl J Med. 2016] the recombinant modified factor Xa (fXa) protein, andexanet alfa, effectively reversed fXa activity in patients presenting with acute major bleeding within 18 hours of receiving a fXa inhibitor. Andexanet alfa is a recombinant modified human fXa developed as a specific reversal agent for direct and indirect fXa inhibitors. It has been shown to rapidly and safely reverse anti-fXa activity in healthy volunteers [Mar F et al. Neurosurgery. 2016]. The purpose of the ANNEXA-4 study was to evaluate the efficacy and safety of andexanet alfa for the reversal of anti-fXa activity and for hemostatic control in patients with acute major bleeding. Patients were eligible if their last dose of fXa inhibitor had been taken within 18 hours. The primary efficacy endpoints were change in anti-fXa activity and clinical hemostatic efficacy through 12 hours. Safety endpoints included, overall safety, thrombotic events, antibody development, and 30-day all-cause mortality. Major bleeding was defined as life-threatening with hemodynamic compromise, critical organ bleeding, bleeding with a hemoglobin drop >2 gm/dL, or bleeding leading to a hemoglobin ≤ 8 gm/dL if no baseline hemoglobin was available. All patients received an intravenous (IV) bolus of andexanet and a 2-hour infusion, the dose differed based on the fXa. Patients who were treated with apixaban or who were > 7 hours from their last rivaroxaban dose received an andexanet as an IV bolus of 400 mg plus an infusion of 480 mg at 4 mg/min. Patients who were on enoxaparin, edoxaban, or who were ≤ 7 hours Official Peer-Reviewed Highlights From ESC Congress 2016 29 http://www.escardio.org/365

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