Abstract 11530: Edoxaban For Pediatric Patients With Cardiac Diseases: A Randomized, Open Label, Multicenter Study

Abstract

Introduction: Standard of care (SOC) anticoagulation for thromboembolism (TE) prevention in patients <18 years old with cardiac disease includes low molecular weight heparins or vitamin K antagonists. Limited data exist comparing direct oral anticoagulants as edoxaban with conventional anticoagulants in this population. Hypothesis: Edoxaban is at least as safe as the current standard-of-care (low molecular weight heparins and/or vitamin K antagonists) with regard to the incidence of major and clinically relevant nonmajor bleeding in pediatric patients with cardiac diseases at risk of thromboembolism. Methods: We performed a phase 3, multinational, prospective, randomized, open-label, blinded-endpoint trial in patients <18 years old with cardiac disease (ENNOBLE-ATE, NCT00687882). Children were randomized 2:1 to age- and weight-based oral edoxaban once-daily versus SOC for 3 months (main study). Randomization was stratified by concomitant use of aspirin and by underlying disease groups, as follow: history of Fontan procedure; Kawasaki disease; heart failure; other. Both groups continued in an extension with edoxaban through 1 year. The primary endpoint was adjudicated International Society on Thrombosis and Haemostasis defined clinically-relevant bleeding (CRB). The main secondary endpoint was a composite of symptomatic TE and asymptomatic intracardiac thrombosis. Results: We randomized 168 children from May 2018 to September 2021. The CRB event rates were similar between groups during the main period. One subject per group experienced a nonmajor CRB. Treatment-emergent adverse events occurred in 46.8% (51/109) with edoxaban and 41.4% (24/58) with SOC. One SOC subject experienced 2 TE events (DVT with PE). In 152 subjects continuing in the extension, one CRB event (0.7%; trauma related) and 4 TEs occurred (2.8%; 2 strokes and 2 coronary artery thromboses and/or myocardial infarctions). Conclusion: Bleeding and TE occurred rarely for both groups and during the extension,suggesting that edoxaban is safe and effective for TE prevention in this population. Once daily edoxaban may provide advantage for children considering difficulties with enoxaparin injections and food and drug interactions with warfarin.