Prior anticoagulation experience, bleeding risk, and safety of factor XI inhibition in atrial fibrillation: an analysis of AZALEA-TIMI 71
Bibliographic record
Abstract
Abstract Background Prior tolerability of anticoagulation may be an indicator of bleeding risk, with implications for future bleeding events with ongoing anticoagulation. Abelacimab is a novel factor XI inhibitor that significantly reduced major/clinically relevant non-major (CRNM) bleeding relative to rivaroxaban in patients with atrial fibrillation (AF) in AZALEA-TIMI 71. Purpose We assessed whether prior anticoagulation experience modifies bleeding risk and the safety of abelacimab relative to rivaroxaban among patients enrolled in AZALEA-TIMI 71. Methods AZALEA-TIMI 71 randomized patients with AF 1:1:1 to one of two monthly abelacimab doses (150 or 90 mg) or to rivaroxaban. For this analysis, the abelacimab doses were pooled. Prior oral anticoagulation (OAC)-experienced patients were those treated with either a direct oral anticoagulant (DOAC) or a vitamin K antagonist (VKA) for ≥60 days prior to trial enrollment. Results Among 1,279 patients, 115 were OAC naïve (9%) and 1,164 (91%) were OAC-experienced (67% DOAC, 28% VKA, 5% both). In the rivaroxaban arm, the rate of major/CRNM bleeding was ~2-fold higher in OAC-naïve patients than in OAC-experienced patients (17.0 vs. 7.8 per 100 patient-years [PY]) (Figure A). In the abelacimab arms, the rates of major/CRNM bleeding were 3.8 and 2.8 per 100 PY in OAC-naïve and OAC-experienced patients, respectively. Abelacimab consistently reduced major/CRNM bleeding both in those without and with prior OAC experience (HR 0.19 [0.07-0.57] and 0.35 [0.24-0.53], respectively; p-int = 0.39), with pattern of greater absolute benefit in the OAC-naïve group (ARR 13.2 vs. 5.1 per 100 PY) (Figure A). Results in the OAC-experienced group were similar irrespective of the type of prior OAC experience (DOAC or VKA) (Figure B). Conclusion Prior OAC experience is an important indicator of bleeding risk among patients with AF. Compared with rivaroxaban, abelacimab consistently reduced the risk of bleeding irrespective of OAC experience, with potential for a greater absolute safety benefit among OAC-naïve patients.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 | 0.003 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".