Factor XI Inhibitors Are a Safer Option for Stroke Prevention | ACC 2025

Factor XI inhibitors are on the rise as a potential breakthrough therapy in treating anticoagulation, as they offer a safer alternative to direct oral anticoagulants (DOACs) for atrial fibrillation patients, according to Christian T. Ruff, M.D., M.P.H., director of general cardiology at Brigham and Women's Hospital and associate professor at Harvard Medical School.

While DOACs are highly effective at preventing strokes, their bleeding risks often limit their use, especially in high-risk patients.

Ruff explained further into this challenge to Managed Healthcare Executive.

“I think what I envision with factor XI inhibition is that I hope they’re as effective as the DOACs. If they’re more effective, great. But the reason we’re not using the DOACs is not because they’re not effective—it’s because the bleeding is intolerable for many patients,” Ruff explained.

Unlike DOACs and Jantoven (warfarin), which interfere with the body’s ability to form clots, Ruff explained that factor XI inhibitors specifically target the clotting pathway involved in thrombosis without disrupting normal blood clotting.

This process has the potential to significantly reduce the risk of severe bleeding, including intracranial hemorrhages.

Ruff shared the main reason patients avoid anticoagulation therapy is not concerns about efficacy but fear of bleeding.

“Bleeding, or the fear of bleeding, drives the entire utilization of anticoagulation,” he said. “It’s not due to concerns about efficacy.”