Optimal strategy for thromboprophylaxis in Fontan circulation: A systematic review and meta- analysis with a focus on ethnic differences

Background and Objectives 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. Methods PubMed, Embase, and Cochrane Library databases were searched to identify studies reporting the thromboembolic and bleeding outcomes of patients with Fontan circulation. Results 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) all showed a trend toward reduced thromboembolic risk, compared with no antithrombotic therapy; however, only warfarin was 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 statistically more effective than warfarin (RR, 0.57; 95% CI, 0.37–0.88; p = 0.01). No significant differences in bleeding risk existed between the aspirin and warfarin groups or between any-thromboprophylaxis and no-thromboprophylaxis groups. Conclusions 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.