3111Genetic variability in PAR4 platelet response in relation to bleeding and ischemic outcomes: a genetic substudy of the TRACER trial
Bibliographic record
Abstract
Background: Protease-activated receptors (PARs) 1 and 4 play a key role in thrombin activation of platelets. PAR1 antagonism with vorapaxar reduces arterial thrombosis and ischemic events with an increased risk of bleeding. Genetic variation in platelet response to thrombin may affect bleeding risk and thrombotic events and may influence the safety and efficacy of PAR antagonism. We have demonstrated that the Thr120 variant of the common single nucleotide polymorphism (SNP) rs773902 in the PAR4 gene is associated with higher PAR4-mediated platelet aggregation in humans compared to the Ala120 variant. In this analysis of the TRACER trial, a randomized study comparing vorapaxar vs. placebo in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS), we investigated the relationship between the rs773902 SNP with major bleeding, ischemic events, safety, and efficacy of vorapaxar. Methods: A total of 6146 TRACER subjects were genotyped for rs773902. Patients were grouped according to alleles G (Ala120) and A (Thr120) pairs. The main outcome of the analysis was GUSTO moderate or severe bleeding at 2 years. Ischemic outcomes of interest were cardiovascular death, myocardial infarction, and stroke.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| 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".