Christian T. Ruff, MD, MPH: Abelacimab Cuts Bleeding Risk Versus Rivaroxaban

A new analysis of the AZALEA-TIMI 71 study showed abelacimab, a novel factor XI inhibitor, achieved consistent reductions in bleeding risk for patients on or off antiplatelet (APT) therapy, compared with rivaroxaban.

Presented at the American Heart Association (AHA) Scientific Sessions 2024, these findings on the effect of abelacimab may offer a potentially safer option for patients with atrial fibrillation (AF) who experience an elevated bleeding risk with traditional anticoagulants.

“I think what a drug like abelacimab allows us to do is confidently be able to treat patients with the antithrombotic therapy that both maximizes their stroke potential from AF, but also protects them from coronary disease,” Christian T. Ruff, MD, MPH, senior investigator of the TIMI Group and director of general cardiology at Brigham and Women’s Hospital, told HCPLive. “Even when you add an antiplatelet agent, so combination anti-thrombotic therapy, you don't see any increased risk of bleeding. That allows us to optimally manage not only our patient's AF but also their comorbidities.”

Abelacimab, a novel, investigational, highly selective, fully human monoclonal antibody, binds to factor XI to block activation and prevent the generation of the activated factor XIa form. AZALEA-TIMI 71, launched in February 2021, enrolled 1287 for a head-to-head comparison of the factor XI inhibitor to a standard-of-care anticoagulant.

Among the study population, 318 (25%) had already received antiplatelet therapy, including aspirin alone (16%), P2Y12 (7%), or dual antiplatelet therapy combining both (2%). Among the population, those treated with antiplatelet therapy had a higher rate of coronary artery disease (70% vs. 42%), previous heart attacks (36% vs. 16%), and peripheral artery disease (15% vs. 11%).

The prespecified analysis revealed a 67% reduction in bleeding for patients on antiplatelet therapy receiving abelacimab 150 mg, compared with rivaroxaban (incidence rate, 3.5% vs. 10.6%). Absolute bleeding rates were higher with the combination of rivaroxaban and antiplatelet therapy, compared with rivaroxaban alone (10.6% vs. 7.7%).

However, Ruff and colleagues noted the bleeding rates treated with abelacimab 150 mg were similar irrespective of antiplatelet therapy use (3.5% vs. 3.1%). Overall, the absolute risk difference between abelacimab 150 mg and rivaroxaban was greater in those on antiplatelet therapy, compared with those not receiving antiplatelet therapy (7.1% vs. 4.6%).

“The promise of factor XI inhibition was to deliver effective therapy to reduce thromboembolic events, but far safer,” Ruff told HCPLive. “I think the AZALEA-TIMI 71 study cements the safety of factor XI inhibition, particularly with abelacimab, that this therapy is far safer than anything we've seen with an anticoagulant.”

Disclosures: Ruff reports no relevant disclosures.

Reference

_{Said SA, Patel SM, Giugliana R, Morrow DA, et al. Bleeding with the FXI Inhibitor Abelacimab compared with Rivaroxaban in Patients on Antiplatelet therapy: A Prespecified Analysis of the AZALEA-TIMI 71 Trial. Presented at the American Heart Association (AHA) Scientific Sessions 2024. Chicago, Illinois. November 16-18, 2024.}