INTRODUCTION: 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.

AREAS COVERED: 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.

EXPERT OPINION: 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.