Early discontinuation of prasugrel or clopidogrel in acute coronary syndromes
Bibliographic record
Abstract
BACKGROUND: In the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial of patients with non-ST-segment elevation acute coronary syndrome managed medically without revascularization, treated with prasugrel versus clopidogrel for less than or equal to 30 months after index acute coronary syndrome, post-hoc analyses showed a divergence of treatment effect in favor of prasugrel after 12 months. Potential influential factors, including a potential late treatment effect after early study drug discontinuation in the intention-to-treat analysis, have not been explored. PATIENTS AND METHODS: We carried out an exploratory, post-hoc analysis of 1436 patients who received at least one dose of the study drug and discontinued the drug 7-365 days after randomization. Kaplan-Meier event rates were evaluated starting at the landmark timepoint of study discontinuation through 2 years of follow-up, and were compared between prasugrel and clopidogrel. RESULTS: The unadjusted rates of the primary composite endpoint of cardiovascular death, myocardial infarction, or stroke were 20.1 versus 24.4% in the prasugrel versus clopidogrel groups (log-rank P=0.069). Similar findings were observed for cardiovascular death (13.3 vs. 18.0%, log-rank P=0.022), and cardiovascular death or myocardial infarction (19.3 vs. 23.3%, log-rank P=0.042). In multivariable analyses, there were no significant differences in the adjusted risk of these outcomes between the prasugrel and clopidogrel groups. CONCLUSION: In this hypothesis-generating analysis, high rates of ischemic events were observed after study drug discontinuation, with a lower frequency of events among patients treated with prasugrel versus clopidogrel that did not persist after multivariable adjustment. This analysis highlights the complexities of ascertaining downstream effects of antithrombotic therapies after drug discontinuation.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 teacher head, 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".