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Record W3009673715 · doi:10.1016/j.jcin.2020.01.219

Routine CYP2C19 Genotyping to Adjust Thienopyridine Treatment After Primary PCI for STEMI

2020· article· en· W3009673715 on OpenAlexfundno aff
Jean‐Sébastien Hulot, Bernard Chevalier, Loïc Belle, Guillaume Cayla, Khalifé Khalifé, F Funck, Romain Berthier, Christophe Piot, Muriel Tafflet, Gilles Montalescot, Hervé Breton, Emmanuel Teíger, Grégoire Dambrin, K. Khalife, Laurent Schmutz, R. Berthier, G. Hannebicque, Thérèse Lognoné, F. De Poli, Nicolas Lhoest, Michel Schneeberger, Nicolas Delarche, A. Faure, Hélène Aelion, M. Godin, Martine Gilard, B. Ritz, Pascal Barraud, Pierre Barnay, Lyassine Nait Saidi, O. Le Dref, Philippe Garot, Grégoire Rangé, Christine Robin, Y. Cottin, Géraud Souteyrand, A. Lafont, Arthur M. Fournier, Patrick Dupouy, John Shayne, Philippe Chapon, C Boureux, Jean‐Pierre Faure, H. Ben Amer, Alain Furber, Olivier Ormezzano, G. Bayet, Gaëtan Karrillon, Louis Maillard, A. Grenzinger, Alexander Avran, R. Koning, D. Dumant, X Lamit, Raphaël Dauphin, Laurent Drogoul, T. Cuisset, Olivier Wittenberg, Jean‐Pascal Peyre, P. Laury, Raphaël Robert

Bibliographic record

VenueJACC: Cardiovascular Interventions · 2020
Typearticle
Languageen
FieldMedicine
TopicAntiplatelet Therapy and Cardiovascular Diseases
Canadian institutionsnot available
FundersMerck Sharp and DohmeServierCanada Excellence Research Chairs, Government of CanadaFondation LeducqNovo NordiskMedicines CompanyActelion PharmaceuticalsBoston Scientific CorporationAmgenBoehringer IngelheimFondation Simone et Cino Del DucaMedtronicFédération Française de CardiologieBayerBristol-Myers SquibbEli Lilly and CompanyAstraZenecaBiotronikAmerican College of Cardiology FoundationPfizerSanofiAbbott VascularAbbott Laboratories
KeywordsPercutaneous coronary interventionThienopyridineMyocardial infarctionClopidogrelMedicinePrasugrelInternal medicineClinical endpointCardiologyConventional PCIGenotypeRandomized controlled trialBiology

Abstract

fetched live from OpenAlex

OBJECTIVES: The aim of this study was to evaluate prospectively the clinical impact of routine transmission of CYP2C19 genotype in the management of acute ST-segment elevation myocardial infarction with primary percutaneous coronary intervention. BACKGROUND: Response to clopidogrel differs widely among patients, notably because of CYP2C19 genetic polymorphisms. METHODS: CYP2C19 genotype (6 alleles) was determined centrally and communicated within 4.1 ± 1.9 days of primary percutaneous coronary intervention in 1,445 patients with ST-segment elevation myocardial infarction recruited at 57 centers in France. CYP2C19 metabolic status was predicted from genotype and served to adjust thienopyridine treatment. The primary endpoint was differences in 12-month outcomes (death, myocardial infarction, and stent thrombosis) between patients with the wild-type genotype or gain-of-function allele (class 1, n = 1,118) and those with loss-of-function (LOF) alleles (class 2, n = 272) who received optimized thienopyridine treatment. RESULTS: inhibition in 85% of patients, with significantly higher use of prasugrel or double-dose clopidogrel. The primary endpoint did not differ between class 1 and class 2 patients (3.31% vs. 3.04%, respectively; p = 0.82). In contrast, carriers of LOF alleles without treatment adjustment had significantly worse outcomes (15.6%; p < 0.05). Bleeding rates were not different between groups. CONCLUSIONS: In a real-world setting, a complete CYPC2C19 genotype can be mostly determined in <7 days using analysis of saliva deoxyribonucleic acid collected during the in-hospital phase among patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. Genotype information led to stronger platelet inhibition treatment in the vast majority of LOF allele carriers and to similar clinical outcomes as in patients carrying the wild-type genotype or gain-of-function allele. (Genotyping Infarct Patients to Adjust and Normalize Thienopyridine Treatment [GIANT]; NCT01134380).

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.008
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.008
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

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.

Opus teacher head0.079
GPT teacher head0.303
Teacher spread0.224 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

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Citations37
Published2020
Admission routes1
Has abstractno

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