Abelacimab Cuts AF Bleeding Risk Across Ages with Christian Ruff, MD, MPH

Abelacimab, a novel factor XI inhibitor, significantly lowered the relative risk of bleeding, compared with rivaroxaban, across a spectrum of ages, with the ability for greater absolute reduction among individuals with atrial fibrillation (AF) aged ≥75 years.1

This analysis of the AZALEA-TIMI 71 trial, presented at the American College of Cardiology (ACC) 2025 Annual Scientific Sessions, showed the absolute risk reduction (ARR) for patients ≥75 was 6.2% compared with 4.2% for those less than 75 years.

In an interview with HCPLive, Christian T Ruff, MD, MPH, TIMI Group senior investigator and director of general cardiology at Brigham and Women’s Hospital, pointed to the available data on undertreatment in patients with AF, particularly age as the ultimate indicator of frailty, medical comorbidities, and concern about bleeding.

“We’re talking about huge differences in bleeding and if you had a drug that was effective, that you could use without worry in patients who were 75–85, that would be a tremendous advance for clinicians and their patients,” Ruff told HCPLive. “If you ask why an elderly patient is not given an anticoagulant, it is often because they are old, frail, and clinicians are worried about bleeding. These results will be very encouraging to healthcare providers.”

AZALEA-TIMI 71 randomized 1287 patients with AF to abelacimab 90 mg or 150 mg monthly or rivaroxaban 20 mg or 15 mg daily across a median follow-up of nearly 2 years. This analysis used Cox proportional hazards to examine major and clinically relevant non-major bleeding by treatment age, older or younger than 75.

Nearly half (49%) of patients were ≥75 at baseline, with these patients reporting a lower body mass index (BMI) and a lower likelihood of being on antiplatelet therapy, but more likely to report creatine clearance ≤50 mL/min than younger patients (P <.001 for each).

Both abelacimab doses reduced the risk of major and clinically relevant non-major bleeding, irrespective of age, compared with rivaroxaban. Those above the age threshold had higher ARRs (7.1% and 6.2%) than those below 75 years (4.7% and 4.2%) in the 90 and 150 mg dose cohorts, respectively.

Notably, abelacimab reduced bleeding risk in patients ≥75, irrespective of renal function, BMI, and the use of concomitant antiplatelet therapy

“I think for the development program of abelacimab, the huge initial advance will be getting data in these populations who we're not treating at all, and they're at consequence for fatal strokes or permanent neurologic disability, loss of independence,” Ruff told HCPLive. “If we could deliver effective and safe therapy to those patients, that would be a remarkable achievement.”

Disclosures: Relevant disclosures for Ruff include Anthos Therapeutics, AstraZeneca, Bayer, Janssen, Novartis, and others.

References

1. Al Said S, Patel SM, Giugliano RP et al. Bleeding with the FXI Inhibitor Abelacimab Compared with Rivaroxaban in Older Individuals with Atrial Fibrillation: Analysis of the AZALEA-TIMI 71 Trial. Presented at: American College of Cardiology (ACC.25) Annual Scientific Session. March 29 – 31, 2025. Chicago, Il.

2. Anthos Therapeutics shares new data from the landmark Azalea-TIMI 71 study demonstrating the factor XI inhibitor Abelacimab significantly reduced bleeding in patients regardless of age or bleeding risk. Anthos Therapeutics. March 29, 2025. Accessed March 31, 2025. https://anthostherapeutics.com/press-release/anthos_2025-03-29_release/.