Efficacy and safety of direct oral anticoagulants in pediatric congenital and acquired heart disease: a systematic review and meta-analysis of randomized controlled trials

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Abstract
Children with congenital and acquired heart disease (CAHD) are at high risk for venous thromboembolism (VTE). Traditional anticoagulants such as vitamin K antagonists (VKAs) and low-molecular-weight heparin (LMWH) present challenges in pediatrics due to burdensome administration, frequent monitoring, and adherence issues. Direct oral anticoagulants (DOACs) have transformed adult anticoagulation, but their role in pediatric CAHD remains uncertain. To evaluate the efficacy and safety of DOACs compared with standard-of-care (SOC) anticoagulation in pediatric patients with CAHD. We systematically searched PubMed, Scopus, Web of Science, and Embase through July 1, 2025. Eligible studies included RCTs comparing DOACs (dabigatran, rivaroxaban, apixaban, edoxaban) with VKAs, LMWH, or aspirin in patients < 18 years with CAHD. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Prespecified subgroup analyses were performed for children with congenital heart disease (CHD). Four RCTs, including 732 patients, were analyzed. In the overall population (patients with congenital and acquired heart disease), DOACs significantly reduced thromboembolic events compared to standard-of-care anticoagulation (RR = 0.42, 95% CI: 0.18–0.97; p = 0.04). In the prespecified congenital heart disease (CHD) subgroup, a trend toward reduced events was observed but did not reach statistical significance (RR = 0.29, 95% CI: 0.06–1.29). Individual thromboembolic outcomes (stroke, pulmonary embolism, deep vein thrombosis, and intracardiac thrombus) were rare, with no significant differences between DOAC and control groups in either the overall population or the CHD subgroup (all p > 0.05). Regarding safety, major bleeding rates were similar between DOAC and control groups in the overall population (RR = 0.91, 95% CI: 0.25–3.35) and the CHD subgroup (RR = 1.36, 95% CI: 0.06–32.65). Clinically relevant non-major bleeding was also comparable between DOAC and control groups overall (RR = 0.62, 95% CI: 0.23–1.68) and in the CHD subgroup (RR = 0.75, 95% CI: 0.19–2.49). DOACs seem to be effective and safe for thromboprophylaxis in pediatric patients with CAHD. They reduce the risk of thromboembolism without increasing bleeding complications. The online version contains supplementary material available at 10.1186/s12959-026-00850-z.

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