Abstract 207: Vorapaxar in Patients with Prior Ischemic Stroke: Primary Results from the Stroke Cohort of the Multinational TRA 2°P-TIMI 50 Trial
Bibliographic record
Abstract
Vorapaxar is an antiplatelet agent that potently inhibits thrombin-mediated activation of the platelet protease-activated receptor (PAR)-1. Phase 2 trials of vorapaxar suggested efficacy with acceptable safety in patients with ischemic stroke. Methods: TRA 2°P–TIMI 50 was a multinational, randomized, double-blinded, placebo-controlled trial of 26449 patients with a history of atherothrombosis randomized to vorapaxar (2.5 mg daily) or matching placebo added to standard therapy, including antiplatelet agents. Patients who qualified with stroke (N=4883) had a history of ischemic stroke in the prior 2 wks to 12 mo. The first efficacy endpoint was the composite of cardiovascular (CV) death, MI, or stroke. After 2 years, the Data and Safety Monitoring Board recommended discontinuation of study treatment in patients with prior stroke. Results: The qualifying stroke was classified as large vessel in 35%, small vessel in 47%, and other in 18%. Background therapy included aspirin in 81%, clopidogrel in 22%, and dipyridamole in 19%. In the stroke cohort, the 3-year rate of CV death, MI, or stroke was not reduced with vorapaxar vs. placebo (13.0% vs. 11.7%, HR 1.03; 95% CI 0.85-1.25), including recurrent ischemic stroke (HR 0.99; 95% CI 0.78-1.25). There were no statistically significant differences in the effect of vorapaxar based on the type or timing of the qualifying stroke, and a borderline interaction based on co-administration of clopidogrel (Figure) The rate of intracranial hemorrhage (ICH) at 3 years was 2.5% with vorapaxar vs. 1.0% with placebo (HR 2.52; 95% CI 1.46-4.36). Conclusions: In patients with prior stroke receiving standard antiplatelet therapy, adding vorapaxar increased the risk of ICH without a reduction in the primary efficacy endpoint or ischemic stroke. These findings add to the accumulating evidence establishing important risks with combination antiplatelet therapy in patients with prior 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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".