Abelacimab vs Rivaroxaban: Bleeding by Age in AZALEA‑TIMI 71

A prespecified AZALEA‑TIMI 71 analysis examined bleeding outcomes by age, comparing monthly subcutaneous abelacimab (90 mg or 150 mg) with daily oral rivaroxaban (20 mg with dose reduction to 15 mg) in atrial fibrillation and focusing on the composite of major or clinically relevant nonmajor (CRNM) bleeding as reported in AZALEA‑TIMI 71. The report presented both overall results and age-stratified findings using prespecified categorical and continuous age approaches.

The publication described AZALEA‑TIMI 71 as a phase 2b randomized clinical trial that assigned 1287 patients with atrial fibrillation to abelacimab 90 mg monthly, abelacimab 150 mg monthly, or rivaroxaban 20 mg daily with a protocol-specified reduction to 15 mg. The trial was conducted from March 2021 to September 2023, with data analysis performed from February to May 2025. Of the randomized participants, 715 (55.6%) were male and 572 (44.4%) were female; 625 (49%) were aged 75 years or older. The primary end point was defined as a composite of major bleeding or CRNM bleeding, and the comparative analyses reported in the article were anchored to the occurrence of those bleeding events over the trial period.

In the overall randomized population, the authors reported that both abelacimab dosing strategies significantly reduced the composite of major or clinically relevant nonmajor (CRNM) bleeding compared with rivaroxaban.

The prespecified age analyses then assessed whether the reported bleeding differences were consistent across older and younger participants.

When the analysis was stratified by age, major or CRNM bleeding was lower with abelacimab than with rivaroxaban in both prespecified strata. Among patients aged 75 years or older, the hazard ratios were 0.32 (95% CI, 0.17-0.60) for abelacimab 90 mg vs rivaroxaban and 0.40 (95% CI, 0.22-0.73) for abelacimab 150 mg vs rivaroxaban; among those younger than 75 years, the hazard ratios were 0.28 (95% CI, 0.12-0.61) and 0.35 (95% CI, 0.17-0.70), respectively, with P for interaction values of .85 and .84 as reported. The authors also reported larger absolute risk reductions per 100 patient-years in patients aged 75 years or older (7.1 and 6.2 per 100 patient-years for abelacimab 90 mg and 150 mg, respectively, vs rivaroxaban) than in younger patients (4.7 and 4.2 per 100 patient-years), and noted that continuous-age modeling suggested bleeding risk increased with age in the rivaroxaban group while remaining stable in the abelacimab groups (P for interaction, .33). Taken together as described, these analyses were reported as showing consistent relative effects across age, alongside larger absolute differences among older participants.

Baseline characteristics indicated differences by age that were described alongside the bleeding analyses: compared with younger participants, those aged 75 years or older had lower body mass index (28 vs 32), were less likely to be taking antiplatelet therapy at baseline (17% vs 32%), and were more likely to have creatinine clearance of 50 mL/min or less (33% vs 8%). In their conclusion, the authors stated that results of ongoing phase 3 trials are necessary to establish the efficacy and benefit-to-risk ratio of abelacimab.

Key Takeaways:

• The article reported that monthly abelacimab (90 mg and 150 mg) was associated with lower major or clinically relevant nonmajor (CRNM) bleeding than daily rivaroxaban in this phase 2b randomized trial population.
• Age-stratified analyses were reported as showing similar relative associations across age groups (no statistically significant age-by-treatment interaction), with larger absolute risk reductions per 100 patient-years described among participants aged 75 years or older.
• The authors concluded that phase 3 trial results are needed to establish abelacimab’s efficacy and overall benefit-to-risk profile as framed in the report.