Abelacimab versus Rivaroxaban in Patients with Atrial Fibrillation.

Summary

In a randomized comparison in AF, monthly abelacimab reduced free factor XI by ~97–99% and cut major/CRNM bleeding by 62–69% versus rivaroxaban, leading to early trial termination. Adverse event profiles were similar across arms.

Key Findings

• Free factor XI reduced by median 99% (150 mg) and 97% (90 mg) at 3 months.
• Major or CRNM bleeding: 3.2 and 2.6 vs 8.4 events/100 person-years (HR 0.38 and 0.31 vs rivaroxaban; P<0.001).
• Adverse event incidence and severity were similar across groups; trial stopped early due to larger-than-expected bleeding reduction.

Clinical Implications

For AF patients at moderate-to-high stroke risk, factor XI pathway inhibition may substantially lower bleeding compared with factor Xa inhibition while maintaining anticoagulant effect; practice may pivot to monthly parenteral options pending efficacy data.

Limitations

• Open-label comparator arm (rivaroxaban) may introduce performance bias.
• Trial stopped early; efficacy outcomes (stroke/systemic embolism) not reported in the abstract.

Future Directions

Confirm stroke prevention efficacy versus DOACs, assess long-term safety, and compare fixed monthly dosing versus oral regimens across diverse AF subgroups (e.g., CKD, frailty).