The researchers found that abelacimab, a Factor XI inhibitor, at a dose of 150 mg monthly, significantly reduced bleeding compared to the standard-of-care anticoagulant, rivaroxaban.
Atrial fibrillation occurs when an individual's heart beats irregularly. Patients with atrial fibrillation are typically prescribed an anticoagulant, or blood thinner, to reduce the risk of stroke. However, many patients with atrial fibrillation are not prescribed anticoagulants or discontinue them due to concerns of increased risk of bleeding complications. Researchers from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, 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 led by the TIMI Study Group, a team of academic researchers at BWH. The Data Monitoring Committee recommended the trial be stopped due to an overwhelming reduction in bleeding compared to stand-of-care treatment. Their full results were presented in a late-breaking science session at the American Heart Association Scientific Sessions 2023 in Philadelphia, Pennsylvania.
"It should be enormously satisfying to the cardiovascular field, patients and providers that Factor XI inhibitors live up to their promise," said Christian Ruff, MD, MPH, director of General Cardiology within the Cardiovascular Division at Brigham and Women's Hospital and principal investigator of the AZALEA-TIMI 71 Study. "Atrial fibrillation is a common medical condition, and the undertreatment of the condition is still one of the greatest unmet needs 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 to date. The team enrolled 1,287 participants across the globe in 95 study sites. Participants were randomized and administered monthly injections of 150 mg abelacimab, 90 mg abelacimab, or a daily dosage of 20 mg rivaroxaban. The team found that the 150 mg dose of abelacimab reduced bleeding that required hospitalization or medical attention by 67%, compared with rivaroxaban. The 90 mg dose of abelacimab reduced the same types of bleeding by 77%. 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 the rates of stroke were low and there were not any significant differences although the trial was not powered for ischemic events.
Established in 1984, the TIMI Study Group is devoted to advancing the knowledge and care of patients suffering from cardiovascular disease and its risk factors. The group has led a variety of cardiovascular trials from phase I to phase IV, enrolling up to 26,000 participants, supported by both industry and the National Health Institutes (NIH).
TIMI group has begun enrolling patients in the phase three 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," says Ruff. "Now we can shift our attention as we await the results of the phase three trials."
Disclosures: Research grants through institution: Anthos, AstraZeneca, Daiichi Sankyo, Janssen and Novartis.
Honoraria for scientific advisory boards and consulting: Altimmune, Anthos, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Janssen, Merck and Pfizer.
Funding: The AZALEA-TIMI 71 trial was sponsored by Anthos Therapeutics.
