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Clopidogrel metaboliser status based on point-of-care CYP2C19 genetic testing in patients with coronary artery disease.

Erlinge, David LU ; James, S; Duvvuru, S; Jakubowski, J A; Wagner, Henrik LU ; Varenhorst, C; Tantry, U S; Brown, P B; Small, D and Moser, B A, et al. (2014) In Thrombosis and Haemostasis 111(5). p.943-950
Abstract
We compared results obtained with the Nanosphere Verigene® 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™ 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 protein reaction units (PRU) (VerifyNow® P2Y12 assay) and VASP PRI (PRI)... (More)
We compared results obtained with the Nanosphere Verigene® 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™ 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 protein reaction units (PRU) (VerifyNow® 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. (Less)
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published
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in
Thrombosis and Haemostasis
volume
111
issue
5
pages
943 - 950
publisher
F K Schattauer Verlag Gmbh
external identifiers
  • pmid:24402637
  • wos:000335541500019
  • scopus:84899706203
ISSN
0340-6245
DOI
10.1160/TH13-09-0767
language
English
LU publication?
yes
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b69b9bd4-781c-4746-b46b-a6e4593fe63a (old id 4291826)
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http://www.ncbi.nlm.nih.gov/pubmed/24402637?dopt=Abstract
date added to LUP
2014-02-06 22:59:54
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2017-01-01 05:46:34
@article{b69b9bd4-781c-4746-b46b-a6e4593fe63a,
  abstract     = {We compared results obtained with the Nanosphere Verigene® 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™ 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 protein reaction units (PRU) (VerifyNow® 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&lt;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.},
  author       = {Erlinge, David and James, S and Duvvuru, S and Jakubowski, J A and Wagner, Henrik and Varenhorst, C and Tantry, U S and Brown, P B and Small, D and Moser, B A and Sundseth, S and Walker, J R and Winters, K J and Gurbel, P A},
  issn         = {0340-6245},
  language     = {eng},
  number       = {5},
  pages        = {943--950},
  publisher    = {F K Schattauer Verlag Gmbh},
  series       = {Thrombosis and Haemostasis},
  title        = {Clopidogrel metaboliser status based on point-of-care CYP2C19 genetic testing in patients with coronary artery disease.},
  url          = {http://dx.doi.org/10.1160/TH13-09-0767},
  volume       = {111},
  year         = {2014},
}