Factor XI inhibitors or Direct Oral Anticoagulants in Atrial Fibrillation: An Updated Meta-Analysis

Direct oral anticoagulants (DOACs) are the preferred anticoagulants across various clinical settings, including atrial fibrillation (AF). However, their use is inevitably associated with an increased risk of bleeding, which carries important prognostic implications.[1] Targeting coagulation factors involved in the intrinsic pathway, such as factor XI (FXI), has been proposed to reduce bleeding while maintaining adequate ischemic protection.[2] Indeed, the intrinsic pathway plays a crucial role in the amplification phase of coagulation, driving the formation of large thrombi and pathological thrombosis, while playing a lesser role in physiological hemostasis.[2] Early phase II trials comparing FXI inhibitors versus DOACs have shown encouraging results, suggesting an improved safety profile of FXI inhibitors. However, these studies were inconclusive regarding their antithrombotic efficacy, due to the low statistical power and the use of mixed doses of FXI inhibitors.[3] A meta-analysis of early phase II trials, stratified by FXI inhibitor dose, raised concerns about whether FXI inhibitors achieve noninferiority in efficacy compared to DOACs across different clinical settings.[4]