Abelacimab versus Rivaroxaban in Patients with Atrial Fibrillation
- Ruff, Christian T. M.D., M.P.H.
- Patel, Siddharth M. M.D., M.P.H.
- Giugliano, Robert P. M.D.
- Morrow, David A. M.D., M.P.H.
- Hug, Bruce M.D., Ph.D.
- Kuder, Julia F. M.A.
- Goodrich, Erica L. M.S.
- Chen, Shih-Ann M.D.
- Goodman, Shaun G. M.D.
- Joung, Boyoung M.D.
- Kiss, Robert G. M.D.
- Spinar, Jindrich M.D., Ph.D.
- Wojakowski, Wojciech M.D., Ph.D.
- Weitz, Jeffrey I. M.D.
- Murphy, Sabina A. M.P.H.
- Wiviott, Stephen D. M.D.
- Parkar, Sanobar M.D.
- Bloomfield, Daniel M.D.
- Sabatine, Marc S. M.D., M.P.H.
ABSTRACT
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.)
Abelacimab versus Rivaroxaban in Atrial Fibrillation
In patients with atrial fibrillation and moderate-to-high risk of stroke, abelacimab, a monoclonal antibody that inhibits activation of factor XI, led to fewer bleeding events than rivaroxaban.