CYP2C19 Polymorphisms and Smoking Status Affects Responsiveness to the Platelet P2Y12 Receptor Antagonist Clopidogrel
Authors
Sang Won Han ; Yong-Jae Kim ; Woo-Keun Seo ; Sungwook Yu ; Hyo Suk Nam ; Sung Sang Yoon ; Seo Hyun Kim ; Jong Yun Lee ; Jun Hong Lee ; Yang-Ha Hwang ; Jun Lee ; Kyung-A Lee ; Kyung-Yul Lee
Citation
Cardiovascular Prevention and Pharmacotherapy, Vol.1(2) : 63-70, 2019
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.