TOPLINE:

Among adults with atrial fibrillation (AF), those who received the factor XI inhibitor abelacimab had a lower risk for major or clinically relevant nonmajor bleeding than those who received the oral anticoagulant rivaroxaban across age groups, with greater absolute risk reductions in older adults, according to a brief report published in JAMA Cardiology.

METHODOLOGY:

• In a prespecified analysis of a phase 2b randomized trial (AZALEA-TIMI 71), researchers compared the risk for bleeding with abelacimab to that with rivaroxaban by age group in patients with AF.
• They included 1287 patients with AF at a moderate-to-high risk for stroke, 55.6% of whom were men. The trial ran between March 2021 and September 2023.
• Patients were randomly assigned to receive either once-monthly subcutaneous abelacimab (90 mg or 150 mg) or once-daily oral rivaroxaban (20 mg; reduced to 15 mg in those with impaired kidney function).
• The primary outcome was major or clinically relevant nonmajor bleeding, with events counted during treatment and up to 60 days after treatment; the median follow-up duration was 2.1 years. Other assessments included gastrointestinal bleeding, ischemic outcomes, and net clinical outcomes.
• Researchers stratified patients by age: younger than 75 years and 75 years or older; 49% of patients were aged 75 years or older.

TAKEAWAY:

• Patients who received either dose of abelacimab had a significantly lower risk for the primary outcome than those who received rivaroxaban, both among those aged 75 years or older (90 mg: hazard ratio [HR], 0.32; 95% CI, 0.17-0.60; 150 mg: HR, 0.40; 95% CI, 0.22-0.73) and those younger than 75 years (90 mg: HR, 0.28; 95% CI, 0.12-0.61; 150 mg: HR, 0.35; 95% CI, 0.17-0.70).
• The risk for bleeding tended to increase with advancing age among patients who received rivaroxaban but remained stable across ages among those who received abelacimab.
• Absolute risk reductions with abelacimab vs rivaroxaban were greater among patients aged 75 years or older (7.1 and 6.2 events per 100 patient-years for 90 mg and 150 mg, respectively) than among younger patients (4.7 and 4.2 events per 100 patient-years, respectively).
• The use of abelacimab reduced the incidence of major bleeding and major gastrointestinal bleeding in both age groups, nearly eliminating the risk for major gastrointestinal bleeding in adults aged 75 years or older. Reductions in net clinical outcome were also noted.

IN PRACTICE:

“Data support the notion that FXI [factor XI] pathway inhibition may prove to be particularly attractive in older patients, as these patients may derive an even greater absolute reduction in bleeding than their younger counterparts,” the researchers wrote.

SOURCE:

This study was led by Samer Al Said, MD, MSc, of the Brigham and Women’s Hospital in Boston. It was published online on February 04 as a brief report in JAMA Cardiology.

LIMITATIONS:

This study was not designed to test efficacy, and phase 3 trials were needed to confirm the benefit to risk ratio of abelacimab. Researchers cautioned that the findings may not apply to patients with frailty.

DISCLOSURES:

This study received funding from Anthos Therapeutics, a Novartis company. One author reported receiving a postdoctoral grant from the German Research Foundation and receiving personal fees from and having current employment with Novartis. Several authors reported receiving grants, honoraria, and consultant fees from and having other financial and nonfinancial ties with multiple organizations including the funding agency.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.