Thromboprophylaxis in Patients With Fontan Circulation

Quick Takes

  • Aspirin, warfarin, and nonvitamin K oral anticoagulants (NOACs) all lower the risk of thromboembolic events compared with no thrombotic therapy.
  • NOACs appear to be the most effective in the prevention of thromboembolic events compared with aspirin and warfarin.
  • Aspirin tended to have the most favorable overall profile, with both a significantly reduced risk of thromboembolic events and a tendency towards lower risk of major bleeding.

Study Questions:

What is the comparative efficacy and safety of aspirin, warfarin, and nonvitamin K oral anticoagulants (NOACs) in a network meta-analysis?


This network meta-analysis included studies published between 2000 and 2022. The primary efficacy endpoint was thromboembolic events. Major bleeding was a secondary safety endpoint. Frequentist network meta-analyses were conducted to estimate the incidence rate ratios (IRRs) of both outcomes. Ranking of treatments was based on probability (P) score.


A total of 21 studies were included, encompassing 26,546 patient-years. The pooled mean age of patients was 9.3 years at the time of inclusion. The pooled mean follow-up duration was 8.1 years. When compared with no thromboprophylaxis, NOAC (IRR, 0.11; 95% confidence interval [CI], 0.03-0.30), warfarin (IRR, 0.23; 95% CI, 0.14-0.37), and aspirin (IRR, 0.24; 95% CI, 0.15-0.39) were all associated with significantly lower rates of thromboembolic events. The network meta-analysis showed no significant differences in the rates of major bleeding between the different agents. Rankings, which simultaneously analyze competing interventions, suggested that NOACs have the highest P score to prevent thromboembolic events (P score 0.921), followed by warfarin (P score 0.582), aspirin (P score 0.498), and no thromboprophylaxis (P score 0.001). Aspirin tended to have the most favorable overall profile.


The authors concluded that aspirin, warfarin, and NOAC are associated with lower risk of thromboembolic events. Recognizing the limited number of patients and heterogeneity of studies using NOACs, the results support the safety and efficacy of NOAC in patients with a Fontan circulation.


Despite a 2014 Pediatric and Congenital Electrophysiology Society (PACES)/Heart Rhythm Society guideline identifying NOAC as a Class III recommendation for patients with Fontan circulation, their use has become relatively common. Some type of thromboprophylaxis (at least aspirin) is recommended for all Fontan patients, and some patients with arrhythmia or other risk factors are recommended full anticoagulation. This study showed safety and efficacy of NOAC in Fontan patients, although there were several limitations to the study. Overall, the Fontan patients were quite heterogeneous in age, ranging from young children to adulthood. The patients were generally young with a pooled mean age of 9 years. Patients on NOAC were generally concentrated in adulthood. Additionally, across the study, Fontan circulation contributed to a very small proportion of the total data of the study (346 out of a total of 26,546 patient-years). Finally, as the majority of the studies in the meta-analysis were nonrandomized, there is the possibility for bias in baseline characteristics (including the indication for anticoagulation). While NOAC provided excellent anticoagulation, the authors did acknowledge that aspirin appeared to have the most favorable profile when weighing both thrombotic risk and bleeding risk.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Cardiac Surgery and CHD and Pediatrics, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Interventions, CHD and Pediatrics and Quality Improvement, Interventions and Structural Heart Disease

Keywords: Anticoagulants, Arrhythmias, Cardiac, Aspirin, Fontan Procedure, Heart Defects, Congenital, Hemorrhage, Pediatrics, Risk, Secondary Prevention, Thromboembolism, Vascular Diseases, Warfarin

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