Abelacimab versus Rivaroxaban in Patients with Atrial Fibrillation

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. ).