Risk factors for serious adverse events related to vitamin K antagonists in children with congenital or acquired heart disease: a prospective cohort study

Abstract

ObjectivesTo assess the occurrence of thrombosis and major bleeding in children with congenital or acquired heart disease (CAHD) treated with VKA and to identify risk factors for these serious adverse events (SAE). Study designAll children enrolled in our VKA dedicated educational program between 2008 and 2022 were prospectively included. The time in therapeutic range (TTR) was calculated to evaluate the stability of anticoagulation. Statistical analysis included Cox proportional hazard models. ResultsWe included 405 patients. Median follow-up was 18.7 (9.3–49.4) months. The median TTR was 83.1 % (74.4 %–95.3 %). No deaths occurred because of bleeding or thrombotic events. The incidences of thrombotic and major bleeding events were 0.9 % (CI95 % [0.1–1.8]) and 2.3 % (CI95 % [0.9–3.8]) per patient year, respectively. At 1 and 5 years, 98.3 % (CI95 % [96.2 %–99.2 %]) and 88.7 % (CI95 % [81.9 % 93.1 %]) of patients were free of any SAE, respectively. Although the mechanical mitral valve (MMV) was associated to major bleeding events (HR = 3.1 CI95 % [1.2–8.2], p = 0.02) in univariate analysis, only recurrent minor bleeding events (HR = 4.3 CI95 % [1.6–11.7], p < 0.01) and global TTR under 70 % (HR = 4.7 CI95 % [1.5–15.1], p < 0.01) were independent risk factors in multivariable analysis. In multivariable analysis, giant coronary aneurysms after Kawasaki disease (HR = 7.8 [1.9–32.0], p = 0.005) was the only risk factor for thrombotic events. ConclusionOverall, VKA therapy appears to be safe in children with CAHD. Suboptimal TTR, regardless of the indication for VKA initiation, was associated with bleeding events.