Bibliographic record
Abstract
Antiplatelet therapy with clopidogrel should be administered to patients with acute coronary syndromes and those submitted to percutaneous coronary intervention (PCI) (secondary prevention). Clopidogrel is a pro-drug which requires hepatic cytochrome P450 (CYP) metabolic activation to produce the active metabolite that inhibits platelet aggregation. CYP2C19 and CYP3A4/5 are the principal contributors in the two-step hepatic oxidation of clopidgrel. However, the response to clopidogrel is not uniform; it varies from patients platelet reactivity on standard-dose clopidogrel are at increased risk of recurrence of adverse cardiovascular events. Also drug-drug interactions that influence the function of CYP isoenzymes may affect the response to clopidogrel. Lipophilic statins, such as atorvastatin, are predominantly metabolized by CYP3A4 and may interfere with CYP activation of clopidogrel, contrary to what happens with hydrophilic statins, such as rosuvastin or pravastatin. Recently, it has been shown that in patients who presented post-PCI high on-treatment platelet reactivity on standard-dose clopidogrel during chronic treatment with clopidogrel and low-dose atorvastatin (10 mg), switching to a non-CYP3A4-metabolized statin, such as rosuvastatin or pravastatin, resulted in a significant decrease in platelet reactivity. The clinical benefit of statins is attributed to mulitple mechanisms which go beyond their lipid-lowering effects and include also antithrombotic properties. In particular, atorvastatin inhibits adenosine diphospate and thrombin-induced platelet aggregation. Moreover, pharmacodynamic studies appear to show some synergy between clopidogrel and atorvastatin: the enhancement of clopidogrel effects due to atorvastatin seems to be dose-related and independent of LDL cholesterol reduction. A recent study shows that the addition of high-dose atorvastatin (80mg) for 30 days significantly improves the pharmacodynamic effects of double-dose clopidogrel, reducing platelet reactivity and improving optimal clopidogrel response in statin naïve patients with high-on treatment platelet reactivity on standard-dose clopidogrel. These pharmacodynamic studies suggest that switching to a no CYP3A4-metabolized statin in patients with high on-treatment platelet reactivity on standard-dose clopidogre on chronic treatment with low-dose atorvastatin or administration of high-dose atorvastatin maybe two alternative strategies to avoid possible negative drug-drug interactions and to improve individual patient response to clopidogrel.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.001 | 0.003 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.975 | 0.979 |
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; the direct Gemma label and the distilled Codex classifier agree on what is shown here.
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".