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

David Erlinge, Stefan James, Suman Duvvuru, Joseph A. Jakubowski, Henrik Wagner, Christoph Varenhorst, Udaya S. Tantry, Patricia B. Brown, David Small, Brian A. Moser, Scott S. Sundseth, Joseph R. Walker, Kenneth J. Winters, Paul A. Gurbel

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish (US)
Pages (from-to)943-950
Number of pages8
JournalThrombosis and Haemostasis
Volume111
Issue number5
DOIs
StatePublished - 2014

Keywords

  • Clopidogrel
  • Genotyping techniques
  • Pharmacogenetics CYP2C19 polymorphisms
  • Prasugrel

ASJC Scopus subject areas

  • Hematology

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