Introduction: Over the past decade, direct oral anticoagulants (DOACs) have become an option for thromboprophylaxis in children with coronary artery aneurysms (CAAs) after Kawasaki disease (KD). Currently, there is limited real-world evidence regarding patterns of usage, effectiveness, and safety of DOACs for this indication.

Methods: We identified patients with KD receiving DOACs reported to the International Kawasaki Disease Registry (IKDR)determine including patterns, effectiveness, and safety.

Results: A total of 41 patients with KD received DOACs (apixaban in >90% of patients) for an average duration of 2.5 years. The earliest documented use of DOACs was in 2018, and the number of treated patients has steadily increased since. Of 138 patients with giant CAAs (z>10) diagnosed and/or still being followed after 2018, 30% had received DOACs at one point during their care, compared to 58 (42%) having received clopidogrel, 77 (56%) enoxaparin, and 25 (18%) warfarin. This is a significant change from patients with giant CAAs discharged before 2018, in which 111/418 (27%) had received clopidogrel, 182 (44%) enoxaparin, and 174 (42%) warfarin. Of the 41 patients who had received DOACs, two received DOACs in the acute phase only, 33 during follow-up only, and six during both phases. Giant CAA were present in 92% of patients who had received DOACs (supergiant (z score >20) in 68%); the use of DOACs in patients with CAA z<10 or in non-CAA patients (during the acute phase for hyperinflammatory prophylaxis) was marginal. Aspirin was used concomitantly with a DOAC in 93% of patients; two also received clopidogrel. CAA thrombosis occurred in 7 (17%) patients prior to their use of DOACs; however, none had thrombosis or bleeding complications while receiving a DOAC.

Conclusions: The use of DOACs in children with KD complicated by CAAs is increasing, particularly in the highest-risk giant CAA patients. This increase seems to be at the expense of warfarin. Despite limited experience, early effectiveness and safety signals are positive, with no reported complications or adverse events with DOAC use in KD.