AUTHOR=Shi Hong Ting , Chen Yong Yuan , Li Xiao Ying , Luo Jian Hua , Zhong Guang Hong , Hu Jia Jia , Zhang Min , Zhou Bo Rong 

TITLE=The Dynamic Effect of Non-CYP3A4-Metabolized and CYP3A4-Metabolized Statins on Clopidogrel Resistance in Patients With Cerebral Infarction

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.738562

DOI=10.3389/fphar.2021.738562

ISSN=1663-9812

ABSTRACT=Objective: To evaluate the dynamic effect of statins in combination with clopidogrel in patients with cerebral infarction (CI).
Methods: One hundred and thirty non-clopidogrel resistant patients were divided into a dynamic clopidogrel resistant (DCR) group and a continuous Non clopidogrel resistance (NCR) group. A total of 98 cases completed all observations and were randomly divided into an AC group (atorvastatin 40 mg/d + clopidogrel, 51 cases) and an RC group (rosuvastatin 20 mg/d + clopidogrel, 47 cases). The patient’s platelet aggregation rate (PAR) was tested using a PL series platelet function analyzer (PL-11) on visit 0 (baseline), visit 1 (one week after clopidogrel alone treatment), and visits 2 to 4 (one, three, and six months after clopidogrel plus statins treatment). The platelet reactivity index (PRI) was assessed using flow cytometry on visits 0, 2, and 4, and liquid chromatography-tandem mass spectrometry was used to monitor clopidogrel thiol metabolite (H4) levels on visits 2 and 4. DNA sequencing was used to determine CYP3A4, CYP2C9, and CYP2C19 genotypes in all patients. Results: The PAR, PRI, and H4 levels of the AC and RC groups were similar (p > 0.05). Compared with the AC group, the DCR ratio of the RC group and the genotype frequencies of CYP2C9*3εC, CYP2C19*2εA, and CYP2C19*3εA were not significantly different (p > 0.05). CYP2C19εA *2 and *3 were independent risk factors for DCR (p < 0.05). 
Conclusion: Clopidogrel combined with atorvastatin (CYP3A4-metabolized) does not affect platelet inhibition by clopidogrel and does not increase the incidence of DCR. The incidence of DCR in the Chinese population is high and is related to CYP2C19εA.