ESC Congress 2016 - 30

clINIcAl TRIAl HIgHlIgHTs from their last rivaroxaban dose received an IV bolus of 800 mg plus an infusion of 960 mg at 8 mg/min. The efficacy population (n = 47) included patients with baseline anti-fXa activity ≥ 75 ng/mL (≥ 0.5 IU/mL for enoxaparin); all patients receiving andexanet were included in the safety population (n = 67). Patients were mostly white men and a mean age of 77 years. Mean time from presentation until andexanet bolus was 4.8 hours (400 mg bolus over 15 minutes). Patients presented with atrial fibrillation, venous thromboembolism, or both. Cardiovascular comorbidities were typical for this population. Bleeding was gastrointestinal (49%), intracranial (~42%), and other (9%). Following bolus treatment with andexanet there was an 89% reduction in anti-fXa rivaroxaban activity (95% CI, 58 to 94), which remained depressed until end of the infusion. At 12 hours, activity remained depressed (69% of baseline; Figure 1). The results were similar for apixaban (93% reduction; 95% CI, 87 to 94; Figure 2). Clinical hemostatic efficacy was adjudicated as excellent or good in 79% (95% CI, 64 to 89) of patients. All subgroups had a similar response rate. Andexanet alfa was safe and well tolerated. Anticoagulation was restarted in 27% of patients within 30 days. Thrombotic events occurred in four patients within 3 days of andexanet and in 12 patients within 30 days, but therapeutic anticoagulation was restarted in only 1 of these patients before a thrombotic event occurred. By 30 days there were 10 deaths, of which 6 were cardiovascular. In conclusion, andexanet alfa rapidly reversed antifXa activity and effective hemostasis was observed in 79% of patients with consistency across all patient subgroups. Thrombotic events occurred at rates consistent with the high-risk profile of these patients. Figure 1. Andexanet Significantly Depresses Rivaroxaban fXa Activity Written by Toni Rizzo Anti-Factor Xa Activity, ng/mL 800 600 400 200 0 Baseline Median Percent change (95% CI) 277.0 End of Bolus End of Infusion 4 Hr 8 Hr 12 Hr 16.8 30.6 177.7 127.1 97.9 -89 (-52 to -94) -86 (-55 to -93) -38 (-27 to -45) -49 (-43 to -57) -64 (-51 to -70) Reproduced from New England Journal of Medicine, Connolly SJ et al. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. 2016; DOI: 10.1056/NEJMoa1607887. Copyright © 2016 Massachusetts Medical Society. Reprinted with permission from the Massachusetts Medical Society. Anti-Factor Xa Activity, ng/mL Figure 2. Andexanet Significantly Depresses Apixaban fXa Activity 500 400 300 200 100 0 Baseline Median Percent change (95% CI) 149.7 End of Bolus End of Infusion 4 Hr 8 Hr 12 Hr 10.3 12.3 103.0 107.1 100.2 -93 (-87 to -94) -97 (-85 to -94) -30 (-27 to -45) -28 (-19 to -38) -31 (-27 to -41) Reproduced from New England Journal of Medicine, Connolly SJ et al. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. 2016; DOI: 10.1056/NEJMoa1607887. Copyright © 2016 Massachusetts Medical Society. Reprinted with permission from the Massachusetts Medical Society. 30 October 2016 Risk Prediction Tool for Identifying Patients in Whom Rule Anticoagulation Can Be Discontinued After Unprovoked VTE Validated in REVERSE II Venous thromboembolism (VTE) is a common, potentially fatal condition. Major VTE must be treated with at least 3 to 6 months of anticoagulation therapy. Thereafter, experts recommend that anticoagulants can be discontinued if the risk of recurrent VTE off of anticoagulants is < 5% at 1 year. In patients with provoked VTE caused by a major transient risk factor, anticoagulants should be stopped (risk of recurrent VTE is < 3% at 1 Year). Whether anticoagulation should be continued in patients with unprovoked VTE or VTE provoked by a minor transient risk factor is uncertain. The 2016 American College of Chest Physicians (ACCP) and 2014 European Society of Cardiology (ESC) guidelines suggest that anticoagulants should be continued indefinitely in patients with unprovoked VTE who do not have high bleeding risk [Kearon C et al. Chest. 2016; Konstantinides S et al. Eur Heart J. 2014]. Individual predictors alone are not adequate to identify high risk patients who can discontinue anticoagulation. The REVERSE I study developed a clinical decision rule (CDR) using the HERDOO criteria to guide the decision of when to stop anticoagulation in patients with unprovoked VTE [Rodger MA et al. CMAJ. 2008]. The study found that all men should continue anticoagulants, whereas women with ≤ 1 HERDOO point can discontinue anticoagulants, resulting in the mnemonic "Men Continue and HERDOO2 rule". The Reverse II study, presented by Marc A. Rodger, MD, Ottawa Hospital, Ottawa, Canada, was conducted medicom-publishers.com/mcr http://www.medicom-publishers.com/mcr

Table of Contents for the Digital Edition of ESC Congress 2016