Renal function and factor XI inhibition in atrial fibrillation: a pre-specified analysis of AZALEA-TIMI 71
Bibliographic record
Abstract
Abstract Background Patients with atrial fibrillation (AF) and renal impairment represent a particularly challenging patient population for anticoagulation given their increased bleeding risk. Abelacimab is a novel factor XI inhibitor that significantly reduced major/clinically relevant non-major (CRNM) bleeding relative to rivaroxaban in patients with AF in AZALEA-TIMI 71. Abelacimab is a monoclonal antibody which has no renal elimination, whereas approximately one-third of rivaroxaban is directly renally excreted. Purpose We assessed the safety of abelacimab vs. rivaroxaban with respect to major/CRNM bleeding in patients with and without chronic kidney disease (CKD) enrolled in AZALEA-TIMI 71. Methods AZALEA-TIMI 71 enrolled patients with AF and randomized them in a 1:1:1 manner to one of two abelacimab doses (150 or 90 mg subcutaneously monthly) or to oral rivaroxaban. The abelacimab dosing arms were pooled for this analysis. Randomization was stratified by CrCl ≤50 mL/min, with rivaroxaban 15 mg administered to those with CrCl ≤50 mL/min and rivaroxaban 20 mg administered to those with CrCl >50 mL/min, without any dose adjustment for abelacimab. Results Among 1,277 patients, 263 (21%) and 1,014 (79%) had a CrCl ≤50 and >50 mL/min at randomization respectively. Despite dose-reduction of rivaroxaban in those with CrCl ≤50 mL/min, the rate of major/CRNM bleeding was ~2-fold higher compared to those with CrCl >50 mL/min receiving full-dose rivaroxaban (13.6 vs. 7.0 per 100 patient-years [PY]) (Figure A). Abelacimab consistently reduced major/CRNM bleeding irrespective of CrCl and dose-reduction of rivaroxaban (HR 0.26 [0.12-0.54] and 0.40 [0.26-0.62] for CrCl ≤50 and >50 mL/min respectively; p-interaction = 0.33), with tendency toward greater absolute benefit in those with CrCl ≤50 mL/min (ARR 10.1 vs. 4.2 per 100 PY). These findings were consistent when examining only major bleeding (Figure B). Conclusion Patients with renal impairment are at higher risk of bleeding despite dose reduction of rivaroxaban. Abelacimab significantly reduces bleeding relative to rivaroxaban irrespective of renal function or rivaroxaban dose-reduction, with potential for greater absolute safety benefit in those with impaired renal function.Figure A Figure B
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.006 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".