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 P2Y(12) 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.
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 P2Y(12) 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.
Authors: Bina Ahmed; Stefan Lischke; Mike De Sarno; Leigh Ann Holterman; Faye Straight; Harold L Dauerman Journal: J Thromb Thrombolysis Date: 2013-07 Impact factor: 2.300
Authors: Richard B Horenstein; Rajnikanth Madabushi; Issam Zineh; Laura M Yerges-Armstrong; Cody J Peer; Robert N Schuck; William Douglas Figg; Alan R Shuldiner; Michael A Pacanowski Journal: J Clin Pharmacol Date: 2014-04-07 Impact factor: 3.126