Turning Up to Eleven: Factor XI Inhibitors as Novel Agents to Maximize Safety and Maintain Efficacy in Thromboembolic Disease.

Within the past decade nonvitamin K oral anticoagulants have emerged as the standard of care for the prevention and treatment of thromboembolic disorders, however safety of anticoagulants remain a concern for many patients and providers. There exists new interest in factor XI inhibition as novel therapeutic target based on observations of lower thrombotic rates and without significant bleed risk in individuals with inherited factor XI deficiency. Several classes of factor XI inhibitors including antisense oligonucleotides, monoclonal antibodies, and small molecule inhibitors have undergone preclinical studies and clinical trials in humans. Both osocimab and IONIS-FXI have been evaluated in patients undergoing orthopedic surgery and demonstrated superiority to enoxaparin without increasing major bleeding. Future studies with both these agents are ongoing, as well as the continued development of other inhibitors of factor XI. Early data regarding factor XI inhibition is encouraging as a potent anticoagulant and may offer a safer alternative compared to therapeutic currently available in contemporary practice for thromboembolic disease.