Efficacy and safety of direct oral anticoagulants in pediatric patients: a systematic review and meta-analysis.

BACKGROUND

Thromboembolic events (TE) are increasingly recognized in pediatric patients, necessitating optimal antithrombotic therapy. While direct oral anticoagulants (DOACs) offer potential advantages over standard of care (SOC) such as heparin, comprehensive evidence regarding their use for treatment and prophylaxis remains limited. Therefore, we performed a systematic review and meta-analysis to assess the efficacy and safety of these two classes of anticoagulants.

METHODS

We searched PubMed, Embase, Web of Science, and ClinicalTrials.gov up to November 27, 2025, for relevant randomized controlled trials (RCTs) comparing DOACs with SOC in pediatric patients. Data were synthesized using fixed- or random-effects models to calculate risk ratios (RRs) with 95% confidence intervals (CIs).

RESULTS

Eight RCTs involving 2,002 pediatric patients were included. In terms of efficacy, DOACs were associated with a significant reduction in TE recurrence in treatment studies (RR = 0.50; 95% CI 0.25-0.99) and TE occurrence in prophylaxis studies (RR = 0.63; 95% CI 0.42-0.95). Regarding safety, major bleeding was comparable to SOC with a favorable trend observed for DOACs (RR = 0.64; 95% CI 0.26-1.55). No significant differences were found in all-cause mortality and serious adverse events.

CONCLUSION

DOACs represent an effective alternative to SOC for the treatment and prevention of thromboembolism in children, demonstrating superior efficacy without increasing the risk of bleeding events.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO https://www.crd.york.ac.uk/PROSPERO/view/CRD42024506541, CRD42024506541.