Impact of CYP2C19*2 on Clopidogrel Response and Cardiovascular Outcomes in ST-segment elevation myocardial infarction Patients

Abstract

Background and Objective: Clopidogrel is essential to prevent cardiovascular events in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Despite adherence to clopidogrel, a significant number of cardiovascular events (CVEs) occur in patients after angioplasty. In this study, we sought to determine the association of CVEs with genetic polymorphisms in CYP2C19*2 (rs4244285) that affect metabolic activation of clopidogrel. Methodology: A prospective cohort study (n=204) was conducted from August 2022 to March 2023 at Khyber Medical University and Kuwait Teaching Hospital in Peshawar, Pakistan. STEMI patients (age 30-75 years, all genders) undergoing PCI were included and followed for 12 months. Genotyping of CYP2C19*2 (rs4244285) was performed by TaqMan assay. CVEs (mortality, stent thrombosis, recurrent MI, ischemic events and stroke) were compared between wild-type and variant genotypes. Statistical analysis used Fisher’s exact test to compare CVEs between wild and mutant group, while binary logistic regression examined the relationship between CVEs and risk factors (SPSS v22). Results: The CYP2C19*2 (rs4244285) GA and AA genotypes were significantly associated with cardiovascular events (CVEs) (p < 0.003), whereas the wild-type GG genotype showed no significant correlation. During the 12-month follow-up after PCI, CVEs included: mortality (n = 10; GG = 2, GA+AA = 8), stent thrombosis (n = 5; GG = 0, GA+AA = 5), recurrent myocardial infarction (n = 9; GG = 1, GA+AA = 8), ischemia-related hospitalizations (n = 17; GG = 1, GA+AA = 16), and cerebrovascular accidents (n = 3; GG = 0, GA+AA = 3) Conclusion: Individuals carrying one or two non-functional CYP2C19*2 (rs4244285) alleles — GA and AA genotypes classified as intermediate and poor metabolizers, respectively— showed a significant association with CVEs. Conversely, subjects with GG genotypes (normal metabolizers) had a significantly lower incidence of CVEs.