Abelacimab Shows Lower Bleeding Risk Than Rivaroxaban among AF patients Across Age Groups: JAMA

A new study published in the Journal of the American Medical Association showed that abelacimab, a factor XI inhibitor, consistently reduced bleeding relative to rivaroxaban across all age groups, with a possibly higher absolute bleeding reduction in older patients with atrial fibrillation (AF).

With today's anticoagulants, older age is a significant risk factor for bleeding. In this demographic, inhibiting factor XI (FXI) may be a safer anticoagulant approach. Thus, this research was set to compare the safety of the new FXI inhibitor abelacimab to rivaroxaban in patients with AF.

Patients with AF were randomly assigned to either oral rivaroxaban (20 mg daily, dosage decrease to 15 mg) or one of two subcutaneous abelacimab doses (90 mg or 150 mg monthly) in the randomized clinical study AZALEA-TIMI 71. In this predetermined analysis, bleeding risk was assessed by age in the phase 2b AZALEA-TIMI 71 trial, both continuously and categorically (less than 75 years versus more than 75 years). The participants received daily oral rivaroxaban (20/15 mg) or monthly subcutaneous abelacimab (90 or 150 mg). The composite of major or clinically relevant nonmajor (CRNM) bleeding served as the main outcome measure.

Of the 1287 patients who were randomly assigned, 715 (55.6%) were men and 572 (44.4%) were women; 625 patients (49%) were 75 years of age or older. Patients 75 years of age or older had a lower body mass index (28 vs. 32), were more likely to have a creatinine clearance of 50 mL/min or less (33% vs. 8), and were less likely to be on antiplatelet treatment at baseline (17% vs. 32%).

When compared to rivaroxaban, both abelacimab doses were linked to significantly less major or CRNM bleeding in patients 75 years of age or older. When compared to patients under 75 years old (4.7 and 4.2 per 100 patient-years, respectively), patients 75 years of age or older tended to see higher absolute risk reductions with abelacimab.

When continuously modeled, bleeding risk was constant in the abelacimab group but tended to rise with age in the rivaroxaban group (P for interaction,.33). Overall, abelacimab consistently reduced bleeding when compared to rivaroxaban, independent of age, with the possibility of a bigger absolute reduction in bleeding with older age.

Reference:

Al Said, S., Patel, S. M., Giugliano, R. P., Morrow, D. A., Goodrich, E. L., Murphy, S. A., Hug, B., Parkar, S., Chen, S.-A., Goodman, S. G., Joung, B., Kiss, R. G., Wojakowski, W., Weitz, J. I., Bloomfield, D., Sabatine, M. S., & Ruff, C. T. (2026). Abelacimab vs rivaroxaban in older individuals with atrial fibrillation: A prespecified analysis of the phase 2b AZALEA-TIMI 71 trial. JAMA Cardiology. https://doi.org/10.1001/jamacardio.2025.5418