Researchers from Mass General Brigham (Boston, USA) have evaluated a drug that represents a new class of anticoagulants known as Factor XI inhibitors for treating patients with atrial fibrillation (AF) as part of the AZALEA-TIMI 71 study—reporting in the New England Journal of Medicine that the Factor XI inhibitor abelacimab (Anthos Therapeutics) significantly reduced bleeding compared to rivaroxaban, a standard-of-care anticoagulant.
The trial was stopped early as per a recommendation from its data monitoring committee due to an “overwhelming” reduction in bleeding compared to standard-of-care treatment, according to the researchers.
“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 (Brigham and Women’s Hospital, Boston, USA), 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.”
Patients with AF are typically prescribed an anticoagulant to reduce their risk of stroke, but many may discontinue them or never receive a prescription due to concerns over an increased risk of bleeding complications.
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 research team enrolled 1,287 participants in 95 study sites across the globe. Participants were randomised and received monthly injections of abelacimab (150mg), abelacimab (90mg), or standard dosing of rivaroxaban (20mg or 15mg in dose reduced patients).
The team found that the 150mg dose of abelacimab reduced bleeding that required hospitalisation or medical attention by 62% compared with rivaroxaban. The 90mg 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—the most common type of bleeding that occurs in patients on currently available anticoagulants—compared to rivaroxaban.
The researchers note 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 ischaemic events.
The TIMI study group is leading an ongoing Phase 3 trial, LILAC-TIMI 76, which will compare the 150mg dose of abelacimab to placebo in high-risk AF patients who have been deemed ineligible for current anticoagulants for the prevention of ischaemic 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,” said Ruff. “Now, we can shift our attention as we await the results of the Phase 3 trials.”
