CLINICAL QUESTION: Can the inhibition of free factor XI with a monoclonal antibody be used for stroke prevention in Atrial fibrillation patients?
BACKGROUND: Atrial fibrillation is a common arrhythmia with a significant risk of stroke, with a need for anticoagulation in most cases. Many direct oral anticoagulants are available, but they have a risk of bleeding. Factor XI is essential for thrombosis but not essential for hemostasis. Therefore, factor XI inhibition should potentially have lower rates of bleeding. Abelacimab is a human monoclonal antibody that binds to the catalytic domain of Factor XI and also inhibits the activated form of the factor.
STUDY DESIGN: Partially blinded, randomized trial. Double-blinded with respect to the two groups who received different doses of abelacimab, but open-label with respect to whether assigned to the abelacimab or rivaroxaban group.
SETTINGS: Study conducted at 95 centers in seven countries from 2021 to 2023, including the U.S., Canada, Hungary, and Korea. Most patients were white. Patients were at least 55 years of age, had atrial fibrillation, and planned for anticoagulation with a CHADS-VASc score of 4+. The median age was 74 years.
SYNOPSIS: From March to Dec 2021, 1,280 patients were randomized to receive one dose of trial therapy. One group received a 150-mg subcutaneous injection of abelacimab, the second received 90 mg of abelacimab, and the third received oral rivaroxaban at 20 mg daily. Free Factor XI levels were measured in both abelacimab groups to ensure a reduction in serum levels was present.
26 patients in the 150-mg abelacimab group and 21 patients in the 90-mg abelacimab group, as compared with 66 patients in the rivaroxaban group, had the primary endpoint of major bleeding. The trial was terminated early in September 2023 because both dose levels of abelacimab relative to rivaroxaban had a lower incidence of major bleeding.
BOTTOM LINE: The trial drug abelacimab demonstrated fewer overall adverse effects of major bleeding compared to rivaroxaban. However, more studies are ongoing to determine stroke prevention for this medication.
CITATION: Ruff CT, et al. Abelacimab versus rivaroxaban in patients with atrial fibrillation. N Engl J Med. 2025;392(4):361-371. doi: 10.1056/NEJMoa2406674.
Dr. Shahatto
Dr. Shahatto is an assistant clinical professor of medicine and a hospitalist at UC San Diego Health in San Diego.