Journal Article

Abelacimab versus Rivaroxaban in Patients with Atrial Fibrillation

Murphy, Sabina A., Bloomfield, Daniel, Giugliano, Robert P., Spinar, Jindrich, Parkar, Sanobar, Goodman, Shaun G., Kuder, Julia F., Patel, Siddharth M., Hug, Bruce, Goodrich, Erica L., Sabatine, Marc S., Morrow, David A., Joung, Boyoung, Kiss, Robert G., Wiviott, Stephen D., Ruff, Christian T., Wojakowski, Wojciech, Weitz, Jeffrey I., Chen, Shih-Ann

2025

Overview

Abelacimab 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. Patients 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. A 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. Among 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.).

• Publisher: Massachusetts Medical Society
• Subject: Administration, Oral / Aged / Aged, 80 and over / Antibodies, Monoclonal, Humanized - administration & dosage / Antibodies, Monoclonal, Humanized - adverse effects / Anticoagulants / Anticoagulants - administration & dosage / Anticoagulants - adverse effects / Anticoagulation / Arrhythmias / Atrial Fibrillation - blood / Atrial Fibrillation - complications / Atrial Fibrillation - drug therapy / Bleeding / Cardiac arrhythmia / Cardiology / Cardiology General / Coagulation / Coagulation factors / Creatinine / Defibrillators / Double-Blind Method / Drug dosages / Embolisms / Factor Xa Inhibitors - administration & dosage / Factor Xa Inhibitors - adverse effects / Factor XI - analysis / Factor XI - antagonists & inhibitors / Female / Fibrillation / Follow-Up Studies / Hematology / Hemorrhage - chemically induced / Hemorrhage - diagnosis / Hemorrhage - epidemiology / Humans / Hypothesis testing / Incidence / Injections, Subcutaneous / Ischemia / Male / Middle Aged / Monoclonal antibodies / Oncology / Pacemakers / Patients / Rivaroxaban - administration & dosage / Rivaroxaban - adverse effects / Severity of Illness Index / Stroke / Stroke - epidemiology / Stroke - etiology / Stroke - prevention & control / Thromboembolism / Thrombosis / Treatment Outcome