Abelacimab Cuts Bleeding Risk in AF Patients Regardless of Kidney Function: AZALEA-TIMI 71 Analysis
USA: A secondary analysis of the AZALEA-TIMI 71 randomized clinical trial, recently published in JAMA Cardiology, has highlighted the potential safety benefits of abelacimab, a novel factor XI inhibitor, compared with rivaroxaban in patients with atrial fibrillation (AF). The findings suggest that abelacimab may offer a more favorable bleeding profile across varying levels of kidney function, including in those with impaired renal health.
The research was led by Siddharth M. Patel and colleagues from the TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, and Harvard Medical School.
Chronic kidney disease is a common comorbidity in patients with AF and poses significant challenges for anticoagulation, as reduced kidney function is associated with elevated bleeding risk. Direct oral anticoagulants (DOACs) like rivaroxaban are widely used, but their renal elimination pathways can complicate dosing and safety outcomes. Against this backdrop, abelacimab—an investigational therapy targeting factor XI—has been evaluated for its ability to minimize bleeding risks while maintaining potential stroke prevention benefits.
In the AZALEA-TIMI 71 trial, 1,284 patients with AF were randomized to receive either rivaroxaban or one of two monthly doses of abelacimab (150 mg or 90 mg). Patients with creatinine clearance (CrCl) below 15 mL/min or on dialysis were excluded. Among participants, the median age was 74 years, and women accounted for nearly 45%. Roughly one-fifth of the cohort had reduced kidney function (CrCl ≤50 mL/min).
The results demonstrated:
- In the rivaroxaban group, patients with impaired kidney function experienced almost double the bleeding rates compared with those with better renal function, despite dose adjustments (13.6 vs 7.0 events per 100 person-years).
- Abelacimab significantly reduced the incidence of major or clinically relevant nonmajor (CRNM) bleeding compared with rivaroxaban, regardless of kidney function.
- Among patients with CrCl ≤50 mL/min, abelacimab reduced bleeding risk with a hazard ratio (HR) of 0.26.
- In patients with CrCl >50 mL/min, the hazard ratio for bleeding with abelacimab was 0.40.
- The absolute risk reduction was greater in patients with impaired renal function (10.1 vs 4.2 events per 100 person-years).
- This safety benefit was consistent not only for major and CRNM bleeding but also for broader measures that included minor bleeding.
- Both abelacimab doses (150 mg and 90 mg monthly) provided similar results.
The investigators emphasized that if abelacimab proves effective for stroke prevention in larger trials, it could be particularly valuable for AF patients with chronic kidney disease, who often face heightened bleeding risks with current therapies.
However, the authors also noted key limitations. The AZALEA-TIMI 71 trial was primarily designed to assess bleeding outcomes, not stroke prevention efficacy. Moreover, since different DOACs vary in their dependence on renal clearance, the findings may not extend to all oral anticoagulants currently in use.
"The prespecified analysis indicates that abelacimab may offer a safer bleeding profile than rivaroxaban across a spectrum of kidney function in patients with AF. While additional research is needed to confirm its efficacy in preventing stroke, the results strengthen the case for factor XI inhibition as a promising therapeutic strategy in this population," the authors concluded.
Reference:
Patel SM, Giugliano RP, Morrow DA, et al. Safety of Factor XI Inhibition With Abelacimab in Atrial Fibrillation by Kidney Function: A Prespecified Analysis of the AZALEA-TIMI 71 Randomized Clinical Trial. JAMA Cardiol. Published online September 01, 2025. doi:10.1001/jamacardio.2025.3393
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