Adverse events in cardiovascular disease patients taking clopidogrel: impact of CYP2C19 genotype polymorphisms

Abstract

Background: Clopidogrel combined with aspirin in antiplatelet therapy is the first-line clinical regimen for cardiovascular diseases. The CYP2C19 gene influences the absorption and metabolism of clopidogrel and its polymorphisms affect antiplatelet therapy drug efficacy, which may lead to adverse events including stent thrombosis and haemorrhage. The main objective of this study was to explore the impact of CYP2C19 polymorphisms on adverse events in cardiovascular disease patients.Methods:We recruited 350 patients taking clopidogrel and performed CYP2C19 genotype testing. Adverse event information was collected through telephone follow-up. According to CYP2C19 genotype results, patients were divided into three groups: poor metabolism (PM) group, extensive metabolism (EM) group and intermediate metabolism (IM) group. The number of adverse events was compared between the three groups using the chi-squared test and the onset time of adverse events was analysed using the log-rank test. The main factors affecting adverse events were analysed using binary logistic analysis.Results: In total, 326 patients were included in the analysis: 143 patients were in the EM group, 129 patients were in the IM group and 54 patients were in the PM group. In this cohort, 127 adverse events were noted, which occurred in 88 patients. There was no significant difference in the occurrence of adverse events between the EM group and PM group (P=0.185). The median survival times of adverse events in the EM, IM and PM groups were 112 days, 137.5 days and 169 days, respectively, with no significant differences between the three groups (P=0.8713).Conclusion:We found that CYP2C19 polymorphisms were not necessarily associated with adverse events in patients with cardiovascular diseases taking clopidogrel. Rather, the main factors influencing the occurrence of adverse events were concomitant diseases such as hypertension, diabetes and hyperlipidaemia.

correlation between CYP2C19 Polymorphisms and recurrent risk in Patients with Ischemic Stroke treated with Clopidogrel in Kurdistan region-Iraq

“…Similar findings were obtained in a study of patients treated with percutaneous coronary intervention (PCI) and dual antiplatelet therapy (DAPT), which indicated a significant link between main adverse cardiovascular events )MACE( and CYP2C19*2, but not CYP2C19*3 (25) . In contrast to the present study's findings, a study in Melbourne, Australia, found that CYP2C19*17 carriers had a higher risk of ischemia events (P=0.04), but CYP2C19*2 and CYP2C19*3 carriers had no significant association with the outcomes including ischemic events (28) . The explanation for the difference between these conflicting results and the findings of the present study , regarding the relation of CYP2C19*2 and *3 polymorphisms with the recurrent risk of stroke, is may be due to the difference in the allelic frequency between populations since it is highest in Asian populations compared to others (26) , as a result the low frequency of CYP2C19*2 and *3 in populations of Australia in the last study was not sufficient to make a strong correlation with the ischemic events.…”