CYP2C19 Polymorphisms and Smoking Status Affects Responsiveness to the Platelet P2Y12 Receptor Antagonist Clopidogrel

초록

Background The “comparison of triflusal and clopidogrel effects in secondary prevention of stroke based on cytochrome P450 2C19 (CYP2C19) genotyping (MAESTRO)” study was a prospective, multicenter, randomized, open-label, and blind genotype trial. We performed a subgroup analysis of the MAESTRO study to explore the relationship between VerifyNow P2Y12 assay with regard to CYP2C19 polymorphisms and smoking status in patients with non-cardiogenic ischemic stroke who underwent clopidogrel treatment. Methods For the study, patients treated with clopidogrel and who underwent VerifyNow P2Y12 assay was selected from the MAESTRO study. Results Of the 393 patients in 18 hospitals, 256 (65%) patients in 12 hospitals were entered for this subgroup analysis. P2Y12 reaction unit (PRU) was significantly lower and percent inhibition (% INH) was higher in the current smoking group than in the nonsmoking group (p<0.001). The same results were also observed in the good genotype group when compared with the poor genotype group (p<0.001). Among the groups, significant lower PRU and higher % INH was demonstrated in current smoking with good genotype group. However, there was no difference in PRU and % INH between current smoking with poor genotype group and nonsmoking with good genotype group, suggesting that clopidogrel activity was concurrently related to CYP2C19 polymorphisms and smoking status. Conclusions Regarding secondary stroke prevention, patients who were current smokers and had a poor genotype for clopidogrel metabolism may benefit from clopidogrel treatment similar to that in patients who were nonsmokers and had a good genotype.

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