CYP2C19 genotypes and their impact on clopidogrel responsiveness in percutaneous coronary intervention

Mejin, Melissa; Tiong, Wen Ni; Lai, Lana Yin Hui; Tiong, Lee Len; Bujang, Adam; Hwang, Siaw San; Ong, Tiong Kiam; Fong, Alan Yean Yip

doi:10.1007/s11096-013-9783-y

Cited by 19 publications

(10 citation statements)

References 41 publications

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“…The metabolic pathway of antidepressant drugs includes CYP450 enzyme complex and GST. Genetic polymorphisms of CYP450 and GST isoenzymes including SNPs, duplications, deletions and gene conversions can cause either increased or reduced enzymatic activity levels [ 32 , 33 ] with potential implication in DILI pathogenesis. Amitriptyline is demethylated mainly by CYP2C19 and CYP3A4 to form the active metabolite nortriptyline which is further metabolized by hydroxylation through the CYP2D6 pathway [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Liver Function Test Abnormalities in Depressed Patients Treated with Antidepressants: A Real-World Systematic Observational Study in Psychiatric Settings

et al. 2016

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BackgroundConcerning the risk of antidepressant induced liver injury, it is not clear whether psychiatrists perform a liver function test (LFT) and whether an increase in aminotransferase levels should contraindicate antidepressant treatment.AimTo evaluate LFT availability, the prevalence of LFT abnormalities and the probable cause of an altered LFT in patients with a major depressive episode (MDE) requiring an antidepressant drug.MethodsWe studied LFT evaluation in a real world psychiatric setting, in a sample of 321 consecutive patients with a current major depressive episode (MDE) requiring an antidepressant drug treatment, but without current alcohol or drug dependence or unstable medical disease.ResultsAn LFT is performed in 36.1% (116/321) of depressed patients. One fifth of antidepressant-treated patients who had an LFT evaluation had abnormal results. The most frequent causes of LFT abnormalities were: NAFLD (nonalcoholic fatty liver disease) (7/321; 2.1%), acute alcohol consumption (4/321; 1.2%), antidepressant-induced liver injury (3/321; 0.9%), hepatitis C virus infection (2/321; 0.6%) and heart failure (1/321; 0.3%). The cause of LFT abnormalities was unknown in 32% of patients (8/25) due to the absence of etiological investigations.ConclusionThese results demonstrate that an LFT is infrequently performed by psychiatrists in depressed patients requiring an antidepressant drug. Baseline LFT assessment and observations during the first six months of antidepressant treatment may be useful for detection of patients with pre-existing liver disease such as NAFLD, and early identification of cases of antidepressant-induced liver injury. An increase in aminotransferase levels may be related to an underlying liver disease, but does not contraindicate antidepressant treatment.

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Section: Discussionmentioning

confidence: 99%

Liver Function Test Abnormalities in Depressed Patients Treated with Antidepressants: A Real-World Systematic Observational Study in Psychiatric Settings

et al. 2016

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“…Although there are consistent literature asserting the association between clopidogrel HTPR and the CYP2C19∗2 and ∗3 LoF alleles, in depth analysis of the data indicated that this association is strong in the PM who are carriers of the homozygous genotypes of the CYP2C19 (∗2/∗2,∗3/∗3) but not for the same extent with the IM who are carriers of the heterozygous genotypes ( ∗1/∗2,∗1/∗3) [4, 91–93]. Furthermore, patients who are EM but suffering from clopidogrel HTPR would be misclassified as responsive (having optimum clopidogrel platelets inhibition) based on their CYP2C19 genotype [94].…”

Section: Adoption Of Pharmacogenetics Biomarkers In Clinical Practicementioning

confidence: 99%

“…They had found that although carriers of one or two alleles of the CYP2C19∗2 had significantly low platelets inhibition while on clopidogrel, low platelets inhibition was found in wild type homozygous carriers CYP2C19 (∗1/∗1) as well. Similarly, Mejin and colleagues had found that there was no significant association between clopidogrel HTPR and CYP2C19 genotype among Malaysian CAD patients [93]. A systematic review and meta-analysis had concluded that, with the exception of stent thrombosis, the CYP2C19 genotype is not significantly associated with cardiovascular events, despite its association with platelets aggregation [95].…”

Section: Adoption Of Pharmacogenetics Biomarkers In Clinical Practicementioning

confidence: 99%

The Personalization of Clopidogrel Antiplatelet Therapy: The Role of Integrative Pharmacogenetics and Pharmacometabolomics

Amin

Chin

Noor

et al. 2017

Cardiology Research and Practice

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Dual antiplatelet therapy of aspirin and clopidogrel is pivotal for patients undergoing percutaneous coronary intervention. However, the variable platelets reactivity response to clopidogrel may lead to outcome failure and recurrence of cardiovascular events. Although many genetic and nongenetic factors are known, great portion of clopidogrel variable platelets reactivity remain unexplained which challenges the personalization of clopidogrel therapy. Current methods for clopidogrel personalization include CYP2C19 genotyping, pharmacokinetics, and platelets function testing. However, these methods lack precise prediction of clopidogrel outcome, often leading to insufficient prediction. Pharmacometabolomics which is an approach to identify novel biomarkers of drug response or toxicity in biofluids has been investigated to predict drug response. The advantage of pharmacometabolomics is that it does not only predict the response but also provide extensive information on the metabolic pathways implicated with the response. Integrating pharmacogenetics with pharmacometabolomics can give insight on unknown genetic and nongenetic factors associated with the response. This review aimed to review the literature on factors associated with the variable platelets reactivity response to clopidogrel, as well as appraising current methods for the personalization of clopidogrel therapy. We also aimed to review the literature on using pharmacometabolomics approach to predict drug response, as well as discussing the plausibility of using it to predict clopidogrel outcome.

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“…Clopidogrel is a prodrug converted to a pharmacologically active anti-platelet agent after metabolism by the CYP2C19 enzyme in the liver. However, in clinical practice, some patients do not achieve the desired anti-platelet action, and some may even show complete clopidogrel resistance resulting in severe adverse events including stent thrombosis, re-myocardial infarction, or death (1). Drug resistance has been attributed to CYP2C19 mutations, which mainly comprise the CYP2C19*2 and CYP2C19*3 alleles.…”

Section: Introductionmentioning

confidence: 99%

Influence of CYP2C19 genotype on antiplatelet treatment outcomes after percutaneous coronary intervention in patients with coronary heart disease

Zhou

et al. 2020

Exp Ther Med

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The aim of the study was to compare the clinical efficacy and safety of ticagrelor and clopidogrel in patients with coronary heart disease one year after percutaneous coronary intervention (PCI), and to explore their association with the CYP2C19 gene polymorphism. A total of 971 patients with coronary heart disease who were hospitalized and underwent PCI from April 2016 to May 2017 were studied. All 971 patients were divided into three subgroups according to CYP2C19 gene types as fast metabolizing, slow metabolizing and very slow metabolizing type. Patients were also classified according to the oral antiplatelet aggregation drugs they received: clopidogrel group and ticagrelor group. The incidence of major adverse cardiac events (MACE) and bleeding events in the clopidogrel-treated and ticagrelor-treated groups and in patients with fast, slow, and very slow CYP2C19 metabolisms were compared. Binary logistic regression analysis was carried out to analyze the risk factors associated with MACEs and hemorrhagic events. Patients on ticagrelor had a greater number of bleeding complications compared to those on clopidogrel (P<0.001), with no difference in MACE between the two groups (P= 0.399). The incidence of MACE was significantly higher in very slow metabolizing patients receiving clopidogrel (P<0.001) while the incidence of bleeding complications was significantly higher in fast metabolizing patients receiving ticagrelor (P<0.001). The regression analysis revealed that the CYP2C19 gene mutation, a dual-antiplatelet therapy, and a stroke history were all significantly associated with MACE. By contrast, a dual-antiplatelet therapy and a stroke history were significantly associated with bleeding events. Findings of the present study indicated that clopidogrel and ticagrelor were equally efficacious post-PCI. Efficacy of clopidogrel was reduced in patients with very slow CYP2C19 genotype while bleeding complications were higher in patients with fast CYP2C19 genotype receiving ticagrelor. CYP2C19 genotyping may be used to provide guidance to optimize individual antiplatelet treatment.

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CYP2C19 genotypes and their impact on clopidogrel responsiveness in percutaneous coronary intervention

Abstract: There was a diverse inter-ethnic difference in the distribution of CYP2C19 polymorphism. The findings of this study echo that of other studies where genotype appears to have a limited impact on clopidogrel responsiveness and clinical outcome in low-risk patients.

Cited by 19 publications

References 41 publications

Liver Function Test Abnormalities in Depressed Patients Treated with Antidepressants: A Real-World Systematic Observational Study in Psychiatric Settings

Liver Function Test Abnormalities in Depressed Patients Treated with Antidepressants: A Real-World Systematic Observational Study in Psychiatric Settings

The Personalization of Clopidogrel Antiplatelet Therapy: The Role of Integrative Pharmacogenetics and Pharmacometabolomics

Influence of CYP2C19 genotype on antiplatelet treatment outcomes after percutaneous coronary intervention in patients with coronary heart disease

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