Author + information
- Received May 5, 2010
- Revision received July 9, 2010
- Accepted July 25, 2010
- Published online October 1, 2010.
- Colin M. Barker, MD⁎,⁎ (, )
- Sarah S. Murray, PhD‡,
- Paul S. Teirstein, MD†,‡,
- David E. Kandzari, MD†,
- Eric J. Topol, MD†,‡ and
- Matthew J. Price, MD†,‡
- ↵⁎Reprint requests and correspondence:
Dr. Colin M. Barker, University of Texas Medical School at Houston, Internal Medicine, Division of Cardiology, 6341 Fannin Street, MSB 2.146, Houston, Texas 77030
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.
Dr. Barker is a consultant and has received speaker honoraria from Cordis and Medtronic. Dr. Murray reports that he has no relationships to disclose. Dr. Teirstein is a consultant and has received research grant support from Abbott Vascular, Medtronic, and Boston Scientific. Dr. Kandzari has received research grant support from Abbott Vascular, Cordis, and Medtronic and is a consultant for Eli Lilly, Medtronic, Cordis, and Abbott Vascular. Dr. Topol is a consultant for Quest Diagnostics and Sanofi-Aventis and is supported by National Institutes of Health/National Center for Research Resources-Clinical and Translational Science Awards Grant ULI RR025774. Dr. Price has received research grant support from Bristol-Myers Squibb, Sanofi-Aventis, and Accumetrics; is a consultant for Bristol-Myers Squibb, Sanofi-Aventis, Accumetrics, Boston Scientific, and Eli Lilly; and has received speaker honoraria from Boston Scientific and Eli Lilly.
- Received May 5, 2010.
- Revision received July 9, 2010.
- Accepted July 25, 2010.
- American College of Cardiology Foundation