Association of
            <i>CYP2C19*2</i>
            Polymorphism with Clopidogrel Response and 1-year Major Adverse Cardiovascular Events in A Multiethnic Population with Drug-Eluting Stents

Chen

et al. 2020

BMC Pharmacol Toxicol

Background: Clopidogrel is an inactive prodrug, it catalyzed into its active form by Cytochrome 450 and Paraoxonase-1(PON-1). polymorphisms of genes encoding these enzymes will affect the efficacy of Clopidogrel. The main objective of our study was to investigate the association of CYP2C19*2, CYP2C19*3 and PON-1Q192R polymorphisms with Clopidogrel resistance and major adverse cardiac events in Jin Hua district in the middle of Zhe Jiang Province in China.Methods: One hundred sixty coronary heart disease patients with percutaneous coronary intervention, who were followed-up for 1 year, were enrolled in our study. These patients were co-administered aspirin 100 mg/d and clopidogrel 75 mg/d following a loading dose of 300 mg. The ADP-induced platelet aggregation rate was measured by Platelet aggregator. Genotypes of CYP2C19*2, CYP2C19*3, PON-1Q192R were determined using Sanger sequencing in all patients. Various clinical data were collected.Results: The frequencies of CYP2C19*2, CYP2C19*3 and PON-1Q192R homozygous mutant genotypes were significantly lower in non-responders than those in responders. After for all variables, CYP2C19*2, CYP2C19*3 and PON-1Q192R independently increased the risk of clopidogrel resistance with adjusted ORs 46.65(95% CI,1.77-25.04; p = 0.005); 22.74(95% CI, 3.11-166.27; p = 0.002); 5.69 (95% CI,1.06-30.47; p = 0.042). Over a follow-up of 12 months, the incidence of major adverse cardiac events (MACE) in CYP2C19*

Section: Introductionmentioning

confidence: 99%

The impact of cytochrome 450 and Paraoxonase polymorphisms on clopidogrel resistance and major adverse cardiac events in coronary heart disease patients after percutaneous coronary intervention

Chen

et al. 2020

BMC Pharmacol Toxicol

Front. Cardiovasc. Med.

“…The relationship between CYP2C19 LOF alleles in patients with AMI using clopidogrel and clinical events has been studied in Northeast Asia, whereas studies in Southeast Asia are limited ( 20 , 21 ). In Taiwan, although the location was near northeast Asian, the island of Southeast Asia (ISEA) ancestry was one of the major genetic ancestries in Taiwan.…”

Section: Discussionmentioning

confidence: 99%

“…The results are consistent with the Singapore cohort ( 21 ), which revealed that LOF patients were significantly more likely to experience MACE compared to non-LOF subjects in acute coronary syndrome (8.0 vs. 5.4%, p = 0.041). In patients without ACS, another smaller cohort in Malaysia recruited patients who underwent elective PCI ( 20 ). The results showed that the presence of the CYP2C19*2 polymorphism was not significantly associated with 1-year MACE after the implantation of DES.…”

Section: Discussionmentioning

confidence: 99%

CYP2C19 loss-of-function alleles predicts clinical outcomes in East Asian patients with acute myocardial infarction undergoing percutaneous coronary intervention and stenting receiving clopidogrel

Chen

Liao

Chang

et al. 2022

BackgroundCYP2C19 loss-of-function (LOF) alleles reduce the effectiveness of clopidogrel and are associated with high rates of clinical events in patients undergoing percutaneous coronary intervention (PCI) and stenting in Northeast Asians. However, the prevalence and influence of CYP2C19 LOF alleles in Southeast Asians remain unclear.ObjectivesThis study aims to retrospectively investigate the prevalence of CYP2C19 LOF alleles and clinical outcomes in East Asian patients taking clopidogrel and undergoing PCI.MethodsBetween June 2019 and June 2020, volunteer participants in a single medical center were consecutively selected. The genetic data of CYP2C19 were derived from the Taiwan Precision Medicine Initiative (TPMI). Patients receiving clopidogrel while undergoing PCI with stenting were retrospectively analyzed.ResultsA total of 999 patients (62.4 ± 11.1 years old, 83.7% men) were enrolled; 39.3% without the CYP2C19 LOF allele (normal metabolizers + rapid metabolizers, NM + RM); 44.9% with one LOF allele (intermediate metabolizers, IM); 15.7% with two LOF alleles (poor metabolizers, PM). The incidence of stroke was higher in the PM subgroup compared to the NM + RM subgroup or IM subgroup in patients presenting with acute myocardial infarction (AMI). The 1-year major adverse cardiac and cerebrovascular events (MACCE)-free survival rates in all participants were similar among the three groups. However, in the AMI group, the 1-year MACCE-free survival rates were significantly lower in the PM subgroup compared to the NM + RM subgroup or IM subgroup.ConclusionIn East Asians presenting with AMI, CYP2C19 PM was associated with deleterious cardiovascular outcomes and stroke. Our results reinforce the crucial role of preemptive CYP2C19 genotyping in East Asian AMI patients receiving clopidogrel treatment.

“…Clopidogrel metabolizes mainly through the cytochrome P450 enzyme system in liver ( 11 ), producing active metabolites, thus inhibiting the platelet aggregation and achieving an anti-platelet effect ( 12 ). Previous findigs have confirmed that ( 13 ) CYP2C19 gene polymorphism is a major factor affecting the anti-platelet effect of clopidogrel.…”

Section: Discussionmentioning

confidence: 99%

Effects of different CYP2C19 genotypes on prognosis of patients complicated with atrial fibrillation taking clopidogrel after PCI

Zhong

et al. 2018

Exp Ther Med

The effects of different cytochrome P450 2C19 (CYP2C19) genotypes on the prognosis of clopidogrel resistance in patients complicated with atrial fibrillation taking clopidogrel after percutaneous coronary intervention (PCI) were investigated. Eighty patients who were complicated with atrial fibrillation and treated with clopidogrel antiplatelet therapy after PCI in Meizhou Hospital Affiliated to Zhongshan University from September 2015 to January 2017 were selected, and divided into two groups according to the CYP2C19 genotype: extensive metabolism (EM) group and poor metabolism (PM) group. The related risk factors of clopidogrel resistance were determined, and the platelet aggregation rate and clopidogrel resistance rate were compared between the two groups during treatment. Non-fatal myocardial infarction and serious life-threatening complications in the two groups were observed. The increased total cholesterol level and the history of smoking and drinking were the independent risk factors of atrial fibrillation after PCI. The platelet aggregation rates in the EM group at 1, 3 and 12 months after medication were significantly lower than those in the PM group in the same period (P<0.05). The clopidogrel resistance rates in EM group before medication and at 1, 3 and 12 months after medication were higher than those in PM group in the same period (P<0.05). The onset time of non-fatal myocardial infarction in EM group was earlier than that in PM group (P<0.05), the infarct area was larger than that in PM group (P<0.05), and the left ventricular ejection fraction (EF) after onset was lower than that in PM group (P<0.05). In conclusion, the increased total cholesterol level and the history of smoking and drinking are the independent risk factors of clopidogrel resistance in patients complicated with atrial fibrillation after PCI. The incidence rates of cardiac complications are increased significantly in patients with PM CYP2C19 genotype.