Optimal Strategy for Thromboprophylaxis in Fontan Circulation: A Systematic Review and Meta-analysis with a Focus on Ethnic Differences

Abstract

Fontan circulation alters cardiovascular hemodynamics to maintain circulation using a single ventricle, which may consequently increase the risk of thromboembolism. This highlights the need for effective thromboprophylaxis strategies. This study assessed optimal thromboprophylaxis regimens for patients with Fontan circulation through a comprehensive meta-analysis of literature focused on personalized, ethnicity-based approaches. PubMed, Embase, and Cochrane Library databases were searched to identify studies reporting the thromboembolic and bleeding outcomes of patients with Fontan circulation. Thirty reports—four randomized controlled trials and 26 cohort studies—were analyzed. Aspirin (risk ratio [RR], 0.46; 95% confidence interval [CI], 0.2–1.08; p = 0.07), warfarin (RR, 0.40; 95% CI, 0.24–0.65; p < 0.001), and direct oral anticoagulants (DOACs) (RR, 0.22; 95% CI, 0.01–7.57; p = 0.4) were compared with no antithrombotic therapy, and only warfarin use resulted in a statistically significant reduction in thromboembolic risk, whereas the effects of aspirin and DOACs were not statistically significant. In the East Asian subgroup, aspirin significantly decreased thromboembolic risk, compared with no intervention (RR, 0.31; 95% CI, 0.16–0.58; p < 0.001), and was significantly more effective than warfarin (RR, 0.57; 95% CI, 0.37–0.88; p = 0.01). Bleeding risk showed no significant between-group differences. Compared with no intervention, thromboprophylaxis in patients with Fontan circulation reduces thromboembolic risk. Although our findings should be carefully interpreted because of the limited data, they indicate that aspirin may be more effective than warfarin in East Asian patients, underscoring the need for further research into ethnicity-tailored thromboprophylaxis strategies.