Edoxaban emerges as effective anticoagulant option in children with cardiac disease, JACC study.

Standard of care (SOC) anticoagulation for thromboembolism (TE) prevention in children with cardiac disease includes low molecular weight heparins or vitamin K antagonists (VKAs). Limited data exists for alternate use of NOACs in children. In the recently published ENNOBLE-ATE trial, authors Portman et al have shown that Edoxaban is a potential alternative mode of thromboprophylaxis in children with cardiac disease showing low rates of clinically relevant bleeding (CRB) and TEs.

Currently, the agents mostly used for thromboprophylaxis in children with cardiac disease are antiplatelets such as aspirin and clopidogrel and anticoagulants such as low-molecular-weight heparin and vitamin K antagonists. DOACs have the advantage of a rapid onset and offset of action, few drug and food interactions, and linear pharmacokinetic variables with no need for routine monitoring.

To obtain safety and efficacy data for edoxaban in children, authors performed a phase 3, multinational, prospective, randomized, open-label, blinded-endpoint trial in patients <18 years of age with cardiac disease.

Patients were randomized 2:1 to age- and weight-based oral edoxaban once daily vs SOC for 3 months (main study period), stratified by cardiac diagnosis. Both groups could continue in an open-label edoxaban extension arm through 1 year. The primary endpoint was adjudicated clinically relevant bleeding (CRB). The main secondary endpoint was symptomatic TE or asymptomatic intracardiac thrombosis.

One patient per group experienced a nonmajor CRB in the main period. Treatment-emergent adverse events occurred in 46.8% with edoxaban and 41.4% with SOC. One SOC patient experienced 2 TE events (DVT with PE).

Among 147 children in the extension, 1 CRB event (0.7%) and 4 TEs occurred.

Edoxaban given once daily offers an attractive advantage to children with cardiac disease and may improve compliance compared with oral vitamin K antagonists. In the current study, the compliance rate was 94% in the edoxaban arm and 45% in the SOC arm.

"Pediatric thrombosis research remains challenging, and the main limitation of this study is the rarity of the primary and secondary outcomes", notes Nadine F. Choueiter in an accompanying editorial.

Source: JACC:

1. J Am Coll Cardiol. 2022 Dec, 80 (24) 2301–2310

2. J Am Coll Cardiol. 2022 Dec, 80 (24) 2311–2313