Coagulation factor XI and coronary artery disease: is there room for factor XI inhibitors?

A growing body of evidence indicates that coagulation factors may exhibit not only prothrombotic, but also proatherogenic effects. Recent years have yielded numerous animal studies demonstrating that factor (F) XI, largely genetically determined, which constitutes a junction between the tissue factor-dependent coagulation and contact pathways may contribute to the development and progression of atherosclerosis. Moreover, an abundancy of FXI may propagate thrombus formation and render dense and lysis-resistant fibrin clots, thus contributing to thromboembolic events such as myocardial infarction (MI) and in particular ischemic stroke. Among FXI inhibitors, asundexian was evaluated in patients following acute MI in a phase 2 randomized PACIFIC AMI trial, without clear benefits from this intervention, while the phase 3 LIBREXIA ACS study aimed to assess milvexian on top of dual antiplatelet therapy in the prevention of secondary ischemic events in high-risk MI survivors was discontinued after interim analysis on basis of futility. The current review summarizes the latest preclinical and clinical studies on the role of FXI in atherogenesis and its thromboembolic manifestations. Moreover, it discusses potential therapeutic options offered by FXI inhibitors.