Article Impact Level: HIGH Data Quality: STRONG Summary of New England Journal of Medicine, 392(4), 361–371. https://doi.org/10.1056/NEJMoa2406674 Dr. Christian T. Ruff et al.
Points
- Abelacimab, a monoclonal antibody targeting factor XI activation, was compared to rivaroxaban for stroke prevention in 1,287 atrial fibrillation patients with moderate-to-high stroke risk.
- Abelacimab significantly reduced significant or clinically relevant nonmajor bleeding events compared to rivaroxaban, with rates of 3.2 (150 mg) and 2.6 (90 mg) events per 100 person-years versus 8.4 for rivaroxaban.
- Abelacimab showed a 99% reduction in free factor XI levels with the 150 mg dose and 97% with the 90 mg dose, outperforming rivaroxaban.
- The trial was stopped early due to abelacimab’s unexpectedly favorable bleeding profile and significantly lower hazard ratios than rivaroxaban (HR for 150 mg: 0.38; HR for 90 mg: 0.31).
- Abelacimab demonstrated a similar safety profile to rivaroxaban while offering a significantly reduced risk of bleeding, positioning it as a promising alternative for atrial fibrillation patients.
Summary
In a recent study comparing abelacimab with rivaroxaban for stroke prevention in atrial fibrillation patients, the safety and efficacy of abelacimab were evaluated. Abelacimab is a fully human monoclonal antibody that inhibits factor XI activation, which plays a crucial role in blood clotting. The trial included 1287 patients with atrial fibrillation and a moderate-to-high stroke risk, randomly assigned to receive either subcutaneous abelacimab (150 mg or 90 mg monthly) or oral rivaroxaban (20 mg daily). The primary endpoint was significant or clinically relevant nonmajor bleeding.
At 3 months, the reduction in free factor XI levels was significantly higher in the abelacimab groups, with a 99% reduction for the 150 mg dose and a 97% reduction for the 90 mg dose. The trial was stopped early due to the unexpectedly favorable bleeding profile with abelacimab. The incidence of major or clinically relevant nonmajor bleeding was notably lower in the abelacimab groups, with rates of 3.2 events per 100 person-years for the 150 mg dose and 2.6 events per 100 person-years for the 90 mg dose, compared to 8.4 events per 100 person-years with rivaroxaban. Hazard ratios for bleeding events were significantly lower with both abelacimab doses compared to rivaroxaban (HR for 150 mg: 0.38, 95% CI 0.24-0.60; HR for 90 mg: 0.31, 95% CI 0.19-0.51, both P<0.001).
These findings suggest that abelacimab is a promising alternative to rivaroxaban for patients with atrial fibrillation. It offers a significantly lower risk of bleeding while achieving a substantial reduction in free factor XI levels. The incidence and severity of adverse events were similar across all treatment groups, supporting the safety profile of abelacimab.
Link to the article: https://www.nejm.org/doi/10.1056/NEJMoa2406674
References Ruff, C. T., Patel, S. M., Giugliano, R. P., Morrow, D. A., Hug, B., Kuder, J. F., Goodrich, E. L., Chen, S.-A., Goodman, S. G., Joung, B., Kiss, R. G., Spinar, J., Wojakowski, W., Weitz, J. I., Murphy, S. A., Wiviott, S. D., Parkar, S., Bloomfield, D., & Sabatine, M. S. (2025). Abelacimab versus rivaroxaban in patients with atrial fibrillation. New England Journal of Medicine, 392(4), 361–371. https://doi.org/10.1056/NEJMoa2406674
