Pilot study of the antiplatelet effect of increased clopidogrel maintenance dosing and its relationship to CYP2C19 genotype in patients with high on-treatment reactivity

Colin M. Barker, Sarah S. Murray, Paul S. Teirstein, David E. Kandzari, Eric J. Topol, Matthew J. Price

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Objectives The objective of this study was to evaluate the antiplatelet effect of clopidogrel 150 mg/day in patients with high on-treatment reactivity (OTR) and to further assess this effect according to CYP2C19 genotype. Background High OTR is associated with ischemic events in clopidogrel-treated patients after percutaneous coronary intervention. Alternative dosing regimens might enhance platelet inhibition. Methods Patients with high OTR receiving a standard clopidogrel regimen were identified with the VerifyNow P2Y12 assay and administered clopidogrel 150 mg daily for 7 days, after which OTR was reassessed. Comprehensive CYP2C19 genotyping was performed with the BeadXpress platform (Illumina, San Diego, California) for the (*)2, (*)3, (*)4, (*)5, (*)6, (*)7, (*)8, and (*)17 variants. Results A total of 41 subjects were enrolled, 20 of whom were carriers of a CYP2C19 loss-of-function (LoF) allele. High-dose clopidogrel significantly reduced OTR from 285 ± 47 P2Y12 reaction units (PRU) to 220 ± 91 PRU (p < 0.001). There were no significant differences in antiplatelet effect according to CYP2C19 status, although the reduction in reactivity was minimal in the small number of patients homozygous for LoF alleles (n = 3, 28 ± 31 PRU, p = NS). Increasing body mass index was independently and negatively associated with the reduction in OTR (p = 0.009). Conclusions In patients with high OTR, clopidogrel 150 mg/day results in a significant reduction in platelet reactivity. Carriage of an LoF CYP2C19 polymorphism does not seem to have a major influence on dose effect. The observed lack of effect in patients with 2 copies of a CYP2C19 LoF allele must be confirmed by larger studies.

Original languageEnglish (US)
Pages (from-to)1001-1007
Number of pages7
JournalJACC: Cardiovascular Interventions
Volume3
Issue number10
DOIs
StatePublished - Oct 2010

Keywords

  • clopidogrel
  • CYP2C19
  • platelet
  • thienopyridine

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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