Factor XI/XIa inhibitors: a potential solution to anticoagulation dilemmas.

Antithrombotic therapy is the cornerstone of stroke prevention, but standard of care therapies are underutilized and use is limited by bleeding rates, drug interactions, and renal elimination. Factor XI/XIa (FXI/XIa) inhibitors are a novel anticoagulation class that purportedly target thrombosis more than hemostasis, thereby raising the hope of reducing bleeding consequences while maintaining efficacy. This review covers the mechanistic rationale for FXI/XIa inhibitors, describes the various molecule sub-classes, addresses barriers to current anticoagulation use, and reviews clinical trial data to date for this novel class of anticoagulants. FXI/XIa inhibitors offer several advantages over DOACs in stroke prevention such as reduced bleeding, fewer drug interactions, and less renal elimination. However, clinical trials must demonstrate non-inferior efficacy and improved safety compared to DOACs. Additional barriers to use will include cost, inadequacy of antidotes, and overall anticoagulant underutilization. The potential for a small molecule or monoclonal antibody to reach the clinic is very high.