Abelacimab Reduces Bleeding in AF Consistently Across Age Groups, With Christian Ruff, MD

Abelacimab, an investigative monoclonal antibody FXI inhibitor, consistently reduced bleeding compared with rivaroxaban in patients with atrial fibrillation (AF) regardless of age, according to a prespecified analysis of the AZALEA-TIMI 71 trial.1

Currently available anticoagulants, such as direct oral anticoagulants (DOACs) or warfarin, are associated with a higher bleeding risk in older patients. In the AZALEA-TIMI 71 trial, investigators compared the safety of abelacimab and rivaroxaban, investigating the former’s potential as an FXI inhibitor for reducing bleeding rates.1

“What was really remarkable was that when you look at both abelacimab doses, you have this low level of bleeding, and it essentially stays there even in patients who are 80, 90 years of age,” Christian Ruff, MD, MPH, director of general cardiology in the cardiovascular division at Brigham and Women’s Hospital, told HCPLive in an exclusive interview. “That’s really important because we’re starting to worry more about lifelong anticoagulation in the elderly. This shows that, as patients age, they’re really not accruing additional risk of bleeding with abelacimab.”

AZALEA-TIMI 71 was a multicenter, randomized, active-controlled phase 2b study conducted at 92 locations worldwide. Investigators enrolled patients ≥55 years old with a history of AF or atrial flutter and planned indefinite coagulation. Additionally, patients with a CHA2DS2-VASc of ≥4 or a CHA2DS2-VASc of ≥3 with either creatinine clearance ≤50 mL/min or planned concomitant use of antiplatelet medication for the duration of the trial were eligible for enrollment.2

Patients were excluded if they had intracranial or intraocular bleeds within the 3 months prior to screening or clinically significant mitral stenosis, defined as a valve area <1.5 cm2. Additionally, those with mechanical heart valves or other indications for anticoagulation therapy besides AF, those with known presence of an atrial myxoma or left ventricular thrombus, and those with a history of left atrial appendage closure or removal, among other criteria, were excluded.2

A total of 1287 patients were enrolled in the trial and were randomly assigned in a 1:1:1 ratio to either blinded subcutaneous adelacimab 150 mg or 90 mg once monthly, or open-label oral rivaroxaban at 20 mg once daily. The rivaroxaban dose was lowered to 15 mg if creatinine clearance was ≤50 mL/min. The study ran from March 2021 to September 2023, with the present data analysis performed from February to May 2025.1

Investigators found that the incidence of major or CRNM bleeding in the rivaroxaban arm was 10.3 per 100 patient-years in those ≥75 years versus 6.7 per 100 patient-years in those <75 years. By contrast, the incidences were 3.2 and 4.1 per 100 patient-years in those ≥75 years and 2 and 2.5 per 100 patient-years among those <75 years in the 90 and 150 mg abelacimab arms, respectively.1

Both doses of abelacimab substantially reduced major or CRNM bleeding versus rivaroxaban, with consistent relative reductions among patients ≥75 years (HR, 0.32; 95% CI, 0.17-0.6; and HR, 0.4; 95% CI, 0.22-0.73; for abelacimab 90 mg and 150 mg vs rivaroxaban, respectively) compared to those <75 years (HR, 0.28; 95% CI, 0.12-0.61; and HR, 0.35; 95% CI, 0.17-0.7; P = 0.85 and 0.84, respectively). These results were consistent irrespective of the threshold for age stratification, such as ≥80 vs <80 years or ≥85 vs <85 years.1

Notably, continuous age analysis showed that major/CRNM bleeding probability gradually increased with advancing age in the rivaroxaban arm but remained stable across all age groups in both abelacimab arms.1

“One of the big challenges that we face in clinical practice is that somewhere between 30 to 50% of patients who have atrial fibrillation either are not started on an anticoagulant or discontinue one. And the primary reason for that is that they have bled before, or they have a fear of bleeding,” Ruff said. “What will make that conversation even easier, though, is if we could say we have a drug that’s associated with 60, 70, 80% less bleeding than anything you’ve used before.”

References

1. Al Said S, Patel SM, Giugliano RP, et al. Abelacimab vs rivaroxaban in older individuals with atrial fibrillation. JAMA Cardiology. Published online February 4, 2026. doi:10.1001/jamacardio.2025.5418

2. Anthos Therapeutics, Inc. Safety and Tolerability of Abelacimab (MAA868) vs. Rivaroxaban in Patients With Atrial Fibrillation (AZALEA-TIMI 71). ClinicalTrials.gov Identifier: NCT04755283. Updated November 6, 2025. Accessed February 6, 2026. https://clinicaltrials.gov/study/NCT04755283