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. (J Am Coll Cardiol 2023;81:771-779) (c) 2023 Published by Elsevier on behalf of the American College of Cardiology Foundation.

Automated summary

FXIa inhibitors have the potential to improve precision in anticoagulation by primarily targeting thrombus formation while sparing clotting and hemostasis. Observational data and small phase 2 trials have shown promising results in terms of bleeding, safety, and prevention of venous thromboembolism. Larger clinical trials are needed to determine the role of FXIa inhibitors in different patient populations.