Real-world use of rivaroxaban for primary thromboprophylaxis and cardiac thrombosis treatment in congenital and acquired heart disease: a prospective cohort study

Abstract To evaluate the incidence of bleeding and thrombotic events in children with congenital or acquired heart disease (CAHD) receiving direct oral anticoagulants by rivaroxaban, and identify associated covariates. This prospective cohort study included children with CAHD treated with rivaroxaban between September 2023 and March 2025, excluding venous thromboembolism. Patients were anticoagulant-naïve or switched from antithrombotic therapy. Serious adverse events (SAE) included significant bleeding events (major bleeding (MB) and clinically relevant non-major bleeding (CRNMB)) and thrombotic events. Cox proportional hazards models were used, with sensitivity analyses excluding patients with prior events under previous antithrombotic therapy. 125 patients were included with: 88(70.4%) patients with Fontan physiology. Seventy-two (58%) patients were switched to rivaroxaban from previous antithrombotic therapy. Median age at initiation was 9.3(IQR:5.5–13.9) years with a median follow-up of 8.5(IQR:3.9–13) months. Twenty SAEs were recorded (3 MB, 13 CRNMB, 4 thrombotic events). The incidences of significant bleeding events and thrombosis event were of 13.9%(95%CI[7,9%–24,4%]) and 4.2%(95%CI[1.6%–11,2%]) per patient year, respectively. At 12 months, 88.9%(95%CI[79.8%–94%]) of patients were free of significant bleeding events. Multivariable analysis identified female gender (HR = 13.2(95%CI[2.8–62.4])) and age > 12 years (HR = 7.1(95%CI[1.9–26.3])) as risk factors for significant bleeding events. Abnormal uterine bleeding accounted for 56.2% of significant bleeding events. Sensitivity analyses yielded similar results. Rivaroxaban therapy appears feasible in children with CAHD, but was associated with higher bleeding and thrombotic events than previously reported in clinical trials. Particular attention should be given to teenage girls at higher risk of abnormal uterine bleeding.