Researchers conducted a study to test a new type of blood thinner called Factor XI inhibitors for atrial fibrillation patients, as part of the AZALEA-TIMI 71 trial. The study was terminated early following the Data Monitoring Committee’s advice, due to a significant decrease in bleeding incidents when compared to the standard treatment.
Patients diagnosed with atrial fibrillation usually receive anticoagulants, medicines that thin the blood, to help lower their chances of having a stroke. However, many patients either don’t start these medications or stop taking them because they worry about the potential for excessive bleeding. Researchers from Mass General Brigham looked at a new class of anticoagulants known as Factor XI inhibitors in their investigation of atrial fibrillation patients during the AZALEA-TIMI 71 Study. The trial was halted early based on recommendations from the Data Monitoring Committee because of a remarkable reduction in bleeding risks compared to traditional treatments. The findings published in the New England Journal of Medicine indicated that abelacimab, a Factor XI inhibitor, significantly lowered bleeding instances compared to the standard blood thinner, rivaroxaban.
Dr. Christian Ruff, MD, MPH, who leads General Cardiology at Brigham and Women’s Hospital and serves as a principal investigator for the study, stated, “It should be extremely rewarding for the cardiovascular field, as well as patients and their healthcare providers, to see that Factor XI inhibitors fulfill their promise of enhanced safety.” He further noted, “Atrial fibrillation is a widespread health issue, and the risk of bleeding associated with existing anticoagulants often leads to inadequate treatment, which remains one of the major obstacles in managing cardiovascular disease.”
Approximately 1 in 3 individuals will develop atrial fibrillation, making it one of the most frequently encountered cardiovascular disorders globally. Patients with this condition face a greatly increased risk of stroke, primarily because blood clots can form in the heart chambers and travel to the brain, resulting in a stroke.
The AZALEA-TIMI 71 Study is the largest and most extended trial examining a Factor XI inhibitor compared to current direct oral anticoagulants. A total of 1,287 participants from 95 study sites worldwide took part in the research. Participants were randomly assigned to receive either 150 mg of abelacimab, 90 mg of abelacimab, or the standard dosage of rivaroxaban (20 mg or 15 mg for those who required a lower dose). Results showed that the 150 mg dose of abelacimab led to a 62% reduction in significant bleeding that required hospitalization or medical assistance, compared to rivaroxaban. The 90 mg dose achieved a 69% reduction in similar bleeding incidents. Furthermore, both dosages of abelacimab nearly eliminated gastrointestinal bleeding, the most common bleeding type associated with current anticoagulants.
In this study, the team observed that stroke rates were low, and there were no notable differences between patients using abelacimab and those on rivaroxaban, although the trial wasn’t designed to specifically measure ischemic events.
The TIMI Study Group is currently running a phase 3 trial called LILAC-TIMI 76, which will investigate the effects of a 150 mg dose of abelacimab against a placebo in high-risk atrial fibrillation patients who have been identified as unsuitable for current anticoagulant therapies in preventing ischemic strokes and systemic embolisms.
Dr. Ruff concluded, “The AZALEA-TIMI 71 Study confirmed that Factor XI inhibitors exhibit a remarkably safe bleeding profile among patients with atrial fibrillation, indicative of a significant breakthrough for our patients. We are now looking forward to the results from the phase 3 trials.”
