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Clopidogrel metaboliser status based on point-of-care CYP2C19 genetic testing in patients with coronary artery disease
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
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2014 (English)In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 111, no 5, 943-950 p.Article in journal (Refereed) Published
Abstract [en]

We compared results obtained with the Nanosphere Verigene (R) System, a novel point-of-care (POC) genetic test capable of analysing 11, CYP2C19 variants within 3 hours, to an established, validated genotyping method (Affymetrix (TM) DMET+; reference assay) for identifying extensive and reduced metabolisers of clopidogrel. Based on genotyping, patients (N=82) with stable coronary artery disease on clopidogrel 75 mg daily were defined as extensive metabolisers (*1/*1, *1/*17,*17/*17), reduced metabolisers (*1/*2,*1/*8,*2/*2,*2/*3), or of indeterminate metaboliser status (*2/*17). Pharmacokinetic exposure to clopidogrel's active metabolite and pharmacodynamic measures with P2Y12 reaction units (PRU) (VerifyNow (R) P2Y12 assay), and VASP PRI (PRI) were also assessed. There was a 99.9% overall; concordance of marker-level data between the Nanosphere Verigene and DMET+ systems in identifying the CYP2C19 variants and 100% agreement in classifying the patients as extensive (n=59) or reduced metabolisers (n=15). Extensive metabolisers had significantly higher active metabolite exposure than reduced metabolisers (LS means 12.6 ng*h/ml vs 7.7 ng*h/ml; p<0.001). Extensive metabolisers also had lower PRU (LS means 158 vs 212; p=0.003) and VASP PRI (LS means 48% vs 63%, p=0.01) compared to reduced metabolisers. Rates of high on-treatment platelet reactivity were higher in reduced metabolisers compared to extensive metabolisers (VASP PRI >= 50%: 79% vs 47%; PRU >235: 33% vs 16%). The Nanosphere Verigene CBS system identified 11 CYP2C19 alleles in less than 3 hours with a high degree of accuracy when compared to a conventional method, and was further validated against pharmacokinetic and pharmacodynamic phenotypes.

Place, publisher, year, edition, pages
2014. Vol. 111, no 5, 943-950 p.
Keyword [en]
Genotyping techniques, clopidogrel, prasugrel, pharmacogenetics CYP2C19 polymorphisms
National Category
Hematology Cardiac and Cardiovascular Systems
URN: urn:nbn:se:uu:diva-227197DOI: 10.1160/TH13-09-0767ISI: 000335541500019OAI: oai:DiVA.org:uu-227197DiVA: diva2:729805
Available from: 2014-06-26 Created: 2014-06-24 Last updated: 2014-06-26Bibliographically approved

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James, Stefan K.Varenhorst, Christoph
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UCR-Uppsala Clinical Research CenterCardiology
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