• Christian T Ruff, Siddharth M Patel, Robert P Giugliano, David A Morrow, Bruce Hug, Julia F Kuder, Erica L Goodrich, Shih-Ann Chen, Shaun G Goodman, Boyoung Joung, Robert G Kiss, Jindrich Spinar, Wojciech Wojakowski, Jeffrey I Weitz, Sabina A Murphy, Stephen D Wiviott, Sanobar Parkar, Daniel Bloomfield, Marc S Sabatine, and AZALEA–TIMI 71 Investigators.
• From the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston (C.T.R., S.M.P., R.P.G., D.A.M., J.F.K., E.L.G., S.A.M., S.D.W., M.S.S.); Anthos Therapeutics, Cambridge, MA (B.H., S.P., D.B.); the Heart Rhythm Center, Taipei Veterans General Hospital and Cardiovascular Center, Taipei, Taiwan (S.-A.C.); Taichung Veterans Hospital, Taichung, Taiwan (S.-A.C.); National Yang Ming Chiao Tung University, Hsinchu, Taiwan (S.-A.C.); National Chung Hsing University, Taichung, Taiwan (S.-A.C.); St. Michael's Hospital, Unity Health Toronto, Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto (S.G.G.); Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada (S.G.G.); the Division of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea (B.J.); the Department of Cardiology, Central Hospital of Northern Pest-Military Hospital, Budapest, Hungary (R.G.K.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (R.G.K.); the Internal Cardiology Department, St. Ann University Hospital and Masaryk University, Brno, Czech Republic (J.S.); the Department of Cardiology and Structural Heart Diseases, Medical University of Silesia, Katowice, Poland (W.W.); the Departments of Medicine and of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada (J.W.); and the Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada (J.W.).
• N. Engl. J. Med. 2025 Jan 23; 392 (4): 361371361-371.

BackgroundAbelacimab is a fully human monoclonal antibody that binds to the inactive form of factor XI and blocks its activation. The safety of abelacimab as compared with a direct oral anticoagulant in patients with atrial fibrillation is unknown.MethodsPatients with atrial fibrillation and a moderate-to-high risk of stroke were randomly assigned, in a 1:1:1 ratio, to receive subcutaneous injection of abelacimab (150 mg or 90 mg once monthly) administered in a blinded fashion or oral rivaroxaban (20 mg once daily) administered in an open-label fashion. The primary end point was major or clinically relevant nonmajor bleeding.ResultsA total of 1287 patients underwent randomization; the median age was 74 years, and 44% were women. At 3 months, the median reduction in free factor XI levels with abelacimab at a dose of 150 mg was 99% (interquartile range, 98 to 99) and with abelacimab at a dose of 90 mg was 97% (interquartile range, 51 to 99). The trial was stopped early on the recommendation of the independent data monitoring committee because of a greater-than-anticipated reduction in bleeding events with abelacimab. The incidence rate of major or clinically relevant nonmajor bleeding was 3.2 events per 100 person-years with 150-mg abelacimab and 2.6 events per 100 person-years with 90-mg abelacimab, as compared with 8.4 events per 100 person-years with rivaroxaban (hazard ratio for 150-mg abelacimab vs. rivaroxaban, 0.38 [95% confidence interval {CI}, 0.24 to 0.60]; hazard ratio for 90-mg abelacimab vs. rivaroxaban, 0.31 [95% CI, 0.19 to 0.51]; P<0.001 for both comparisons). The incidence and severity of adverse events appeared to be similar in the three groups.ConclusionsAmong patients with atrial fibrillation who were at moderate-to-high risk for stroke, treatment with abelacimab resulted in markedly lower levels of free factor XI and fewer bleeding events than treatment with rivaroxaban. (Funded by Anthos Therapeutics; AZALEA-TIMI 71 ClinicalTrials.gov number, NCT04755283.).Copyright © 2025 Massachusetts Medical Society.

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