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

Published

Journal Article

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 P2Y12 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.

Full Text

Duke Authors

Cited Authors

  • Erlinge, D; James, S; Duvvuru, S; Jakubowski, JA; Wagner, H; Varenhorst, C; Tantry, US; Brown, PB; Small, D; Moser, BA; Sundseth, SS; Walker, JR; Winters, KJ; Gurbel, PA

Published Date

  • May 2014

Published In

Volume / Issue

  • 111 / 5

Start / End Page

  • 943 - 950

PubMed ID

  • 24402637

Pubmed Central ID

  • 24402637

Electronic International Standard Serial Number (EISSN)

  • 2567-689X

International Standard Serial Number (ISSN)

  • 0340-6245

Digital Object Identifier (DOI)

  • 10.1160/th13-09-0767

Language

  • eng