Clinical Evaluation of Factor XIa Inhibitor Drugs: JACC Review Topic of the Week.

Factor XI/XIa (FXI/FXIa) represents a potential target for improved precision in anticoagulation because it is involved primarily in thrombus formation and plays a much smaller role in clotting and hemostasis. This suggests that the inhibition of FXI/XIa could prevent pathologic thrombi from forming, but largely preserve a patient's ability to clot in response to bleeding or trauma. This theory is supported by observational data showing that patients with congenital FXI deficiency have lower rates of embolic events without an increase in spontaneous bleeding. Small phase 2 trials of FXI/XIa inhibitors have offered encouraging data with regard to bleeding and safety and evidence of efficacy for the prevention of venous thromboembolism. However, larger clinical trials across multiple patient groups are needed for this emerging class of anticoagulants to understand their possible role in clinical use. Here we review the potential clinical indications for FXI/XIa inhibitors, data available to date, and consider future trials.