Use of factor XI/XIa inhibitors in patients with atrial fibrillation: Current progress and future prospects

Stroke prevention is one of the pillars of management in elderly patients with atrial fibrillation (AF), hence effective and safe anticoagulation strategies are needed. While available anticoagulants target coagulation factors involved in thrombus formation, their bleeding complications and limitations in aging populations underscore the necessity for novel agents. Factor XI/XIa (FXI/XIa), which selectively targets the intrinsic coagulation pathway, offers a promising approach by attenuating thrombin generation without impairing hemostasis. Various novel inhibitors, including antisense oligonucleotides, monoclonal antibodies and small molecules, have been developed. Clinical trials have shown favorable safety profiles with reduced bleeding risks compared to traditional anticoagulants. Some efficacy in preventing thromboembolic events has also been demonstrated, with ongoing trials further evaluating long-term safety and efficacy. This narrative review explores the potential of FXI/XIa inhibitors as a novel anticoagulant approach for AF. We discuss the rationale, pharmacology, evidence and future directions to assess the application prospects of FXI/XIa inhibitors in elderly AF patients, highlighting their potential to improve anticoagulation therapy by decoupling thrombosis prevention from bleeding complications.