Direct oral anticoagulants in children with giant coronary artery aneurysms from Kawasaki disease: a systematic review and meta-analysis

Background To evaluate the comparative efficacy and safety profile of direct oral anticoagulants (DOACs) vs. conventional anticoagulation in children with Kawasaki disease (KD)-associated Giant coronary artery aneurysms (GCAAs). Methods Databases searched included PubMed (MEDLINE), Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from conception until October 2025. Studies that (1) enrolled patients younger than 19 years with documented KD-associated GCAAs; (2) administered DOACs; (3) reported at least one efficacy/safety outcome, were included. Efficacy outcomes included thromboembolic events (coronary thrombosis, myocardial infarction, systemic thromboembolism). Safety outcomes included major or Clinically Relevant Non-Major (CRNM) bleeding. A random-effects model was used to estimate the pooled effects. Results Five studies [two randomized clinical trials (RCTs), two observational studies and one prospective interventional trial] were included with a total of 594 patients [DOACs: 474 (79.8%); standard of care, SOC: 120 (20.2%)]. The overall risk ratio of thromboembolic events for patients on DOACs vs. SOC was not statistically significant [RR 0.27 (95% CI: 0.02–3.17); p = 0.29]. The estimated pooled major or CRNM bleeding event rate was similar [DOACs: Proportion 0.001 (95% CI: 0.00–0.01)] vs. SOC: Proportion 0.03 (95% CI: 0.01–0.07). In the two RCTs, the estimated risk ratio between DOACs vs. SOC was not statistically significant [RR 0.26 (95% CI: 0.05–1.49); p = 0.13]. Conclusion DOACs have potentially non-inferior efficacy and safety profiles compared to conventional agents, supporting the use of DOACs as a first-line anticoagulation strategy in one of childhood's most serious cardiovascular conditions. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251004094 , PROSPERO CRD420251004094.