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

Sze Kiat Alan Ong; Deepan Raj; Anika W Xuen Lee; Liang Shen; Kian Keong Poh; Pei Lin Koh; Swee Chye Quek

doi:10.3389/fcvm.2026.1777856

April 10, 2026Frontiers in Cardiovascular MedicineOpen Access

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

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Why the study?

The comparative efficacy and safety profile of direct oral anticoagulants versus conventional anticoagulation in children with Kawasaki disease-associated giant coronary artery aneurysms needed evaluation.

Do direct oral anticoagulants (DOACs) provide non-inferior efficacy in preventing thromboembolic events and safety regarding major or clinically relevant non-major bleeding compared to conventional anticoagulation in children with Kawasaki disease-associated giant coronary artery aneurysms?

Key Points

To evaluate the comparative efficacy and safety profile of direct oral anticoagulants versus conventional anticoagulation in children with Kawasaki disease-associated giant coronary artery aneurysms.
Searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception through October 2025.
Identified studies of patients younger than 19 years with Kawasaki disease-associated giant coronary artery aneurysms receiving direct oral anticoagulants and reporting efficacy or safety outcomes.
Pooled comparative treatment effects using a random-effects model.
Direct oral anticoagulants demonstrated potentially non-inferior efficacy compared to conventional anticoagulants in preventing thromboembolic events such as coronary thrombosis and myocardial infarction.
Safety profiles concerning major bleeding or clinically relevant non-major bleeding were potentially non-inferior between direct oral anticoagulants and conventional regimens.

Structured PICO

Do direct oral anticoagulants (DOACs) provide non-inferior efficacy in preventing thromboembolic events and safety regarding major or clinically relevant non-major bleeding compared to conventional anticoagulation in children with Kawasaki disease-associated giant coronary artery aneurysms?

P

Population

594 pediatric patients (<19 years old) across 5 studies (2 RCTs, 1 retrospective cohort, 1 case series, 1 prospective interventional study) requiring anticoagulation, including patients with Kawasaki disease (KD)-associated giant coronary artery aneurysms (GCAAs, defined as coronary artery diameter ≥8 mm absolute dimension or Z-score ≥10). Note: in the two RCTs, the majority of the population required anticoagulation for indications other than KD (total 97 KD participants across all 5 studies).

I

Intervention

Direct oral anticoagulants (DOACs: apixaban, edoxaban, or rivaroxaban; n=474, 79.8%), with variable concomitant antiplatelet (aspirin) use across studies.

C

Comparator

Standard of care (SOC) conventional anticoagulation (vitamin K antagonists such as warfarin or low-molecular-weight heparin; n=120, 20.2% in the 2 RCTs), with variable concomitant aspirin use.

O

Outcome

Primary efficacy outcome: thromboembolic events (coronary thrombosis, myocardial infarction, systemic thromboembolism). Primary safety outcomes: major bleeding (defined by ISTH criteria: fatal bleeding, symptomatic bleeding in critical areas, or hemoglobin drop ≥2 g/dL or requiring ≥2 units blood transfusion) or clinically relevant non-major (CRNM) bleeding (overt bleeding not meeting major criteria but requiring medical intervention).composite

Limitations

Limited number of included RCTs (only 2), neither of which was adequately powered for superiority or non-inferiority, necessitating inclusion of observational studies
Majority of the patient population in the two RCTs required anticoagulation for indications other than Kawasaki disease, and attempts to obtain KD-specific subgroup data were unsuccessful
Low event rates for primary outcomes (thromboembolic and major bleeding events) leading to reduced statistical power
Heterogeneity in the types of DOACs used, concomitant antiplatelet reporting, and definitions of outcomes across studies
Relatively short follow-up durations in most studies, precluding evaluation of late thrombotic complications and long-term safety outcomes beyond 5 years

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Implication

This systematic review and meta-analysis suggests that direct oral anticoagulants have comparable efficacy and safety profiles to conventional anticoagulation in children with Kawasaki disease-associated giant coronary artery aneurysms, supporting their potential use as a more convenient first-line anticoagulation strategy.

Abstract

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. 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.

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Cite This Study

Ong et al. (2026) studied this question.

synapsesocial.com/papers/69fe79fcd8476229fea35ae0 https://doi.org/10.3389/fcvm.2026.1777856

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

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Key Points

Structured PICO

Limitations

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Implication

Abstract

Discussion

Cite This Study

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

Figures

Key Points

Structured PICO

Limitations

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Implication

Abstract

Discussion

Cite This Study

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