Key result
CYP2C19 abnormal metabolizer status was associated with fewer patients remaining free of cardiac events at 1 year compared to normal metabolizers.
Why the study?
Allelic variation in the CYP2C19 gene impairs clopidogrel metabolism and can lead to MACE, motivating evaluation of CYP2C19 allelic variations in post-PCI patients.
Does CYP2C19 abnormal metabolizer genotype increase the risk of major adverse cardiovascular events in ischemic heart disease patients taking clopidogrel after percutaneous coronary intervention?
Cross-Sectional (n=102)
Yes
Does CYP2C19 abnormal metabolizer genotype increase the risk of major adverse cardiovascular events in ischemic heart disease patients taking clopidogrel after percutaneous coronary intervention?
In Egyptian patients undergoing PCI, abnormal CYP2C19 metabolizer genotypes are highly prevalent (51%) and are associated with a significantly increased risk of major adverse cardiovascular events while on clopidogrel therapy.
Answers are grounded in this paper and cite their sources.
May inform clopidogrel risk stratification post-PCI; hypothesis-generating and requires prospective trials before practice change.
BACKGROUND: Cardiovascular diseases (CVDs) are considered a leading cause of death worldwide. Allelic variation in the CYP2C19 gene leads to a dysfunctional enzyme, and patients with this loss-of-function allele will have an impaired clopidogrel metabolism, which eventually results in major adverse cardiovascular events (MACE). Ischemic heart disease patients (n = 102) who underwent percutaneous cardiac intervention (PCI) followed by clopidogrel were enrolled in the present study. METHODS: The genetic variations in the CYP2C19 gene were identified using the TaqMan chemistry-based qPCR technique. Patients were followed up for 1 year to monitor MACE, and the correlations between the allelic variations in CYP2C19 and MACE were recorded. RESULTS: During the follow-up, we reported 64 patients without MACE (29 with unstable angina (UA), 8 with myocadiac infarction (MI), 1 patient with non-STEMI, and 1 patient with ischemic dilated cardiomyopathy (IDC)). Genotyping of CYP2C19 in the patients who underwent PCI and were treated with clopidogrel revealed that 50 patients (49%) were normal metabolizers for clopidogrel with genotype CYP2C19*1/*1 and 52 patients (51%) were abnormal metabolizers, with genotypes CYP2C19*1/*2 (n = 15), CYP2C19*1/*3 (n = 1), CYP2C19*1/*17 (n = 35), and CYP2C19*2/*17 (n = 1). Demographic data indicated that age and residency were significantly associated with abnormal clopidogrel metabolism. Moreover, diabetes, hypertension, and cigarette smoking were significantly associated with the abnormal metabolism of clopidogrel. These data shed light on the inter-ethnic variation in metabolizing clopidogrel based on the CYP2C19 allelic distribution. CONCLUSION: This study, along with other studies that address genotype variation of clopidogrel-metabolizing enzymes, might pave the way for further understanding of the pharmacogenetic background of CVD-related drugs.
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Shawky et al. (2023) conducted a cross-sectional in Acute coronary syndromes (n=102). CYP2C19 abnormal metabolizer status vs. CYP2C19 normal metabolizer status was evaluated on No cardiac events at 1 year (p=0.004). CYP2C19 abnormal metabolizer status was associated with fewer patients remaining free of cardiac events at 1 year compared to normal metabolizers.
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