Risk and benefit trade-off of thromboprophylaxis in patients with Fontan circulation: insights from the National Database of Health Insurance Claims of Japan

Abstract

Background Patients with Fontan circulation are at an increased risk of developing thromboembolic events in the first 3–12 months after surgery [1,2]. Thromboembolic events can lead to significant mortality [3]. The current guidelines recommend the use of antithrombotic therapy, either aspirin or warfarin, as a primary thromboprophylaxis [4,5]. On the other hand, the main adverse effect of thromboprophylaxis is bleeding, which may increase the risk of death. However, there are limited data to assess the outcomes of the thromboembolic and bleeding complications of thromboprophylaxis. Therefore, this retrospective cohort study aimed to evaluate the safety and efficacy of thromboprophylaxis after Fontan surgery. Methods We identified 1903 patients who underwent Fontan surgery between June 2011 and September 2019 from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. The patients were followed-up from 2 months to 1 year after Fontan surgery to assess the primary outcomes of thromboembolic and bleeding events. Moreover, we identified the factors associated with primary outcomes in this population using multivariate logistic regression analysis. Results A total of 1903 patients (56.1% male) underwent Fontan surgery at a median age of 3 years (1–22); 1815 patients (95.4%) had an extracardiac conduit. No thromboprophylaxis was prescribed to 65 patients (3.4%), whereas 228 patients (12.0%) received aspirin alone, 346 patients (18.2%) received warfarin alone, and 1264 patients (66.4%) received a combination therapy of aspirin and warfarin. In the first post-operative year, thromboembolic events occurred in 234 patients (12.3%) and bleeding events occurred in 202 patients (10.6%). Older age (odds ratio, 1.08; 95% confidence interval, 1.06–1.11) and aspirin use (odds ratio, 0.34; 95% confidence interval, 0.15–0.78) were independently associated with thromboembolic events. In particular, up to 5 months after surgery, the incidence rate of thromboembolism was significantly lower in patients who received aspirin alone (0.9%) than in those who received other thromboprophylaxis regimens (no thromboprophylaxis, 13.8%; warfarin, 7.5%; combination therapy, 7.4%; p<0.05). No significant difference in incidence of bleeding events was observed among the four thromboprophylaxis regimens. A history of postoperative hemorrhage (odds ratio, 1.49; 95% confidence interval, 1.01–2.21) and the use of a potassium channel blocker (odds ratio, 2.12; 95% confidence interval, 1.10–4.05) was associated with a higher risk of bleeding events. Conclusions In this study, patients who received aspirin alone showed a significantly lower incidence of thromboembolic events. Aspirin may be useful for preventing thromboembolism a year after Fontan surgery. After Fontan surgery, it is important to select a safe and effective thromboprophylaxis regimen and evaluate the risk factors for thromboembolic and bleeding events in a timely manner. Funding Acknowledgement Type of funding sources: None.