Patients with atrial fibrillation are typically prescribed an anticoagulant, or blood thinner, to reduce the risk of stroke, but many may discontinue them or never receive a prescription due to concerns of increased risk of bleeding complications. Researchers from Mass General Brigham evaluated a drug that represents a new class of anticoagulants known as Factor XI inhibitors for treating patients with atrial fibrillation as part of the AZALEA-TIMI 71 Study. The trial was stopped early by the recommendation of the Data Monitoring Committee due to an overwhelming reduction in bleeding compared to standard-of-care treatment. The researchers report in the New England Journal of Medicine that abelacimab, a Factor XI inhibitor, significantly reduced bleeding compared to a standard-of-care anticoagulant, rivaroxaban.
“It should be enormously satisfying to the cardiovascular field, patients and providers that Factor XI inhibitors live up to their promise of superior safety,” said Christian Ruff, MD, MPH, director of General Cardiology within the Cardiovascular Division at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, senior investigator in the TIMI Study Group and principal investigator of the AZALEA-TIMI 71 Study. “Atrial fibrillation is a common medical condition, and bleeding with currently available anticoagulants resulting in significant undertreatment is still one of the greatest shortcomings in cardiovascular disease.”
About 1-in-3 people will develop atrial fibrillation, making it one of the most common cardiovascular conditions in the world. The risk of stroke increases significantly in patients with atrial fibrillation because blood clots form in the heart chambers and can be pumped to the brain, causing a stroke.
The AZALEA-TIMI 71 Study is the largest and longest trial examining a Factor XI inhibitor compared to standard of care direct oral anticoagulants to date. The team enrolled 1,287 participants in 95 study sites across the globe. Participants were randomized and administered monthly injections of 150 mg abelacimab, 90 mg abelacimab, or standard dosing of rivaroxaban (20 mg or 15 mg in dose reduced patients). The team found that the 150 mg dose of abelacimab reduced bleeding that required hospitalization or medical attention by 62%, compared with rivaroxaban. The 90 mg dose of abelacimab reduced the same types of bleeding by 69%. In addition, the team found that both doses of abelacimab almost eliminated gastrointestinal bleeding compared to rivaroxaban, which is the most common type of bleeding that occurs in patients on currently available anticoagulants.
The team notes that in the AZALEA-TIMI 71 Study, the rates of stroke were low and there were not any significant differences between patients in the abelacimab groups compared to those taking rivaroxaban, although the trial was not powered for ischemic events.
The TIMI Study Group is leading an ongoing phase 3 trial of the study, LILAC-TIMI 76, which will compare the 150 mg dose of abelacimab to placebo in high-risk atrial fibrillation patients who have been deemed ineligible for current anticoagulants for the prevention of ischemic stroke and systemic embolism.
The AZALEA-TIMI 71 Study validated that Factor XI inhibitors have an incredibly safe bleeding profile in patients with atrial fibrillation, which is a tremendous potential advance for our patients. Now we can shift our attention as we await the results of the phase 3 trials.”
Christian Ruff, MD, MPH, Director of General Cardiology within the Cardiovascular Division, Brigham and Women’s Hospital
Source:
Journal reference:
Ruff, C. T., et al. (2025) Abelacimab versus Rivaroxaban in Patients with Atrial Fibrillation. New England Journal of Medicine. doi.org/10.1056/NEJMoa2406674.
