[Factor XI inhibition in atrial fibrillation: where do we stand?]

Abstract

Factor XI (FXI) has emerged as a promising target in the prevention and treatment of venous and arterial thromboembolism in several clinical settings. Its pharmacological inhibition, through small molecules, monoclonal antibodies, antisense oligonucleotides and small-interfering RNA, has been developed with the aim of achieving effective anticoagulation while reducing bleeding risk compared to conventional anticoagulants. Phase II studies have explored the role of FXI inhibitors in surgical thromboprophylaxis, in non-valvular atrial fibrillation (AF), and as an adjunctive strategy in acute atherothrombotic settings such as acute coronary syndromes and ischemic stroke. Although preliminary data on these compounds suggest an encouraging safety profile, the available evidence regarding efficacy remains less than convincing. The phase II AZALEA-TIMI 71 trial was terminated early after showing a significant reduction in the incidence of major bleeding with abelacimab compared with rivaroxaban. In contrast, the phase III OCEANIC-AF trial of asundexian was halted due to inferiority versus apixaban. Ongoing trials, such as LILAC-TIMI 76 and LIBREXIA-AF, will be crucial to further clarify the true efficacy and safety profile of this therapeutic class. While FXI inhibitors represent a potential innovation in the treatment of AF, additional evidence is required to clearly and definitively define their role in clinical practice. This review aims to examine the pathophysiological rationale underlying the use of FXI inhibitors, to describe the different molecular subclasses currently under development, and to summarize the results of both completed and ongoing clinical trials of this novel therapeutic class, with the goal of outlining future perspectives for thromboembolic prevention in patients with AF.