Use of factor XI inhibitors compared with DOACs in atrial fibrillation and thromboembolism prevention: a systematic review and meta-analysis of randomized-controlled trials

Background Anticoagulation therapy needs to be chosen considering individual patient characteristics to prevent thromboembolic events while minimizing the risk of bleeding. Direct Oral Anticoagulants (DOACs) are standard therapy in patients with high risk of these events and meet criteria for anticoagulation. Factor XI (FXI) inhibitors have arisen such as a new drug class with low bleeding potential. However, comparison of efficacy and safety between these two classes of medication still remains uncertain. Purpose To compare FXI and DOACs in patients with high risk of thromboembolic outcomes, evaluating its efficacy and safety. Methods PubMed, Embase and Cochrane database were searched for randomized controlled trials that compared inhibitors of FXI to DOACs for high risk patients, and reporting the following outcomes of safety: (1) Major bleeding and (2) Clinically Relevant Non-major Bleeding (CRNMB), and those of efficacy: (3) Stroke and (4) Systemic Embolism . We computed pooled Risk Ratio (RR), adopting a random-effects model and 95% confidence intervals (CI) .Statistical analysis was performed using R statistical software (4.2.2). Heterogeneity was assessed using the I² statistical. Results We included 17,317 patients from 4 RCTs, of whom 52.8% were undergoing treatment with FXI inhibitors. The patients’ mean age was 73.7±7.54 years and 36.7% were female. The occurrence of major bleeding was significantly lower in patients using FXI inhibitors compared to DOACs (RR 0.32, 95% CI 0.21-0.47, p<0.001, Fig. 1A). Similarly, FXI inhibitors group statistically decreased risk of CRNMB, compared to DOACs group (RR 0.46, 95% CI 0.36-0.59, p< 0.001, Fig. 1B). However, stroke incidence was higher in the FXI group when compared to DOACs group (RR 3.3, 95% CI 1.89-5.85, p<0.001, Fig. 2A); and systemic embolism was not statistically significant between groups(RR 2.69, 95% CI 0.62-11.67, p=0.18 Fig. 2B) Conclusion Our data show the safety profile of FXI inhibitors in relation to DOACs, with a reduction in bleeding episodes. However, the efficacy of using FXI in patients at high risk of thromboembolic events is lower compared to DOACs. More randomized controlled studies are needed to elucidate the effectiveness of FXI inhibitors.