Time-Varying Effects of Prasugrel Versus Clopidogrel on the Long-Term Risks of Stroke After Acute Coronary Syndromes
Bibliographic record
Abstract
BACKGROUND AND PURPOSE: The role of more intense, sustained platelet inhibition in preventing stroke after acute coronary syndrome (ACS) is unclear. We observed a signal for reduced stroke risk in the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial after 12 months of treatment with prasugrel versus clopidogrel in medically managed patients with ACS. METHODS: We examined 7243 patients with ACS, aged <75 years and without prior stroke, analyzing differences in baseline characteristics between patients with and without a stroke event through 30 months with a Cox proportional hazards model. We also assessed the effect of prasugrel versus clopidogrel (plus aspirin) on risk of all stroke events and ischemic stroke over time with an extended Cox proportional hazards model. RESULTS: Stroke events were infrequent through 30 months (ischemic stroke=62; hemorrhagic stroke=15). Patients with stroke were older, had more comorbidities, and had a higher Global Registry of Acute Coronary Events (GRACE) risk score. There was a trend for a lower unadjusted frequency of all stroke events through 30 months for prasugrel versus clopidogrel: 31 (1.5%) versus 46 (2.2%); P=0.08. There was a significant treatment-by-time interaction for those with ischemic stroke (P=0.03), consistent with the 12-month landmarked Kaplan-Meier log-rank test showing a reduced hazard of ischemic stroke after 12 months with prasugrel (P=0.04). No significant interactions between treatment effect of prasugrel versus clopidogrel and time were observed for all stroke events. CONCLUSIONS: We observed a potential late treatment effect for prasugrel versus clopidogrel for a reduced risk of ischemic stroke in medically managed patients with ACS aged <75 years. These hypothesis-generating findings suggest that longer duration and more potent platelet inhibition with prasugrel may be associated with lower risk of ischemic stroke after 12 months. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00699998.
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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 | 0.007 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".