CYP2C19<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:msup><mml:mrow /><mml:mrow><mml:mo>⁎</mml:mo></mml:mrow></mml:msup></mml:mrow></mml:math>2 Polymorphism in Chilean Patients with In-Stent Restenosis Development and Controls

Ruedlinger, Jenny; Prado, Yalena; Zambrano, Tomás; Saavedra, Nicolás; Bobadilla, Braulio; Potthoff, Marcelo; Pérez, Luis Alberto Santos; Lanas, Fernando; Salazar, Luis A.

doi:10.1155/2017/5783719

Cited by 9 publications

(8 citation statements)

References 43 publications

(43 reference statements)

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“…The findings from this study show that despite a higher proportion of CYP2C19*2 allele carriers exhibiting coronary ISR within 1 year compared to non-carriers, and *2 allele carriers being 4.08-times more likely to exhibit ISR than non-carriers, the association between CYP2C19*2 allele carrier status and development of coronary ISR was not statistically significant (p > 0.05). Our findings are similar to Nozari et al 25 who reported that the prevalence of ISR after PCI was higher in *2 allele carriers but without a statistically significant relationship, and contrast to Ruedlinger et al, 26 who identified non-carriers of the *2 allele with higher incidence of coronary ISR.…”

Section: Discussionsupporting

confidence: 90%

“…23,24 With respect to coronary ISR, a 2015 case-match study in an Iranian patient population indicated that the prevalence of ISR during a 1-year period after PCI was higher in patients who were carriers of CYP2C19*2; however, the association did not reach statistical significance. 25 In contrast, in a recent study by Ruedlinger et al, 26 undertaken in Chilean patients who underwent PCI, noncarriers of the CYP2C19*2 allele had a higher incidence of ISR.…”

Section: Introductionmentioning

confidence: 86%

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CYP2C19*2 Allele Carrier Status and Coronary In-stent Restenosis: Is There an Association?

Wirth¹,

Zahra²,

Xuereb³

et al. 2018

Journal of Exploratory Research in Pharmacology

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Background and objective: The CYP2C19*2 allele is associated with reduced clopidogrel bioactivation, increasing the risk of complications after percutaneous coronary intervention (PCI), particularly stent thrombosis. Recently published data suggests that CYP2C19*2 allele carriers have a higher risk for in-stent restenosis (ISR) after endovascular treatment. Very few studies have investigated the relationship between CYP2C19*2 and coronary ISR, with no significant association reported. The objective of this study was to assess the relationship between CYP2C19*2 allele carrier status and coronary ISR. Methods: Patients with previous PCI with stenting and who were scheduled for elective PCI after coronary angiogram were recruited from the cardiac catheterization suite over a 12-month period. The angiography report of each patient was perused to identify patients requiring PCI due to ISR. For patients with angiography-confirmed ISR, date of previous PCI to the restenosed stent was noted. CYP2C19*2 genotyping was undertaken using a TaqMan ® Drug Metabolism assay. The association between CYP2C19*2 allele carrier status and incidence of coronary ISR within 1 year was assessed using Fisher's exact test (p < 0.05 significance) and by calculating the odds ratio (OR) with a 95% confidence interval (CI). Results: Of the 82 patients with previous PCI, 29 (35.4%) had angiography-confirmed ISR (12 carriers, 17 noncarriers of CYP2C19*2). In 13 (44.8%) of these patients, the restenosed stent was deployed within 1 year and the patients were on clopidogrel therapy at the time of repeat PCI (8 carriers, 5 non-carriers of CYP2C19*2). The association between CYP2C19*2 allele carrier status and ISR within 1 year was not statistically significant (Fisher's exact p = 0.067; OR: 4.80, 95% CI: 0.98-23.54, p = 0.053). Conclusions: Despite a higher proportion of CYP2C19*2 allele carriers exhibiting ISR within 1 year compared to non-carriers, the association was not statistically significant. This result may be attributed to the small sample size, and larger prospective studies are recommended to further assess this association.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 86%

CYP2C19*2 Allele Carrier Status and Coronary In-stent Restenosis: Is There an Association?

Wirth¹,

Zahra²,

Xuereb³

et al. 2018

Journal of Exploratory Research in Pharmacology

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“…[20,21] Few studies have been conducted to explore the association between the CYP2C19 *2 allele and incidence of coronary ISR in patients receiving clopidogrel, and con icting ndings have been reported. [22][23][24][25][26] Three studies showed a higher frequency of ISR in carriers of CYP2C19*2 however the correlation was not statistically signi cant [22][23][24] while another study reported a lower incidence of ISR among carriers of CYP2C19*2. [25] These studies concluded that the ndings could be attributed to a small sample size and recommended further analysis.…”

Section: Introductionmentioning

confidence: 99%

“…[22][23][24][25][26] Three studies showed a higher frequency of ISR in carriers of CYP2C19*2 however the correlation was not statistically signi cant [22][23][24] while another study reported a lower incidence of ISR among carriers of CYP2C19*2. [25] These studies concluded that the ndings could be attributed to a small sample size and recommended further analysis.…”

Section: Introductionmentioning

confidence: 99%

CYP2C192* genetic polymorphism and incidence of in-stent restenosis in patients on clopidogrel: a matched case-control study

Osama

Wirth

Zahra

et al. 2021

Drug Metabolism and Personalized Therapy

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Objectives The cytochrome P450 2C19*2 (CYP2C19*2) genetic polymorphism is associated with reduced clopidogrel bioactivation, increasing the risk of atherothrombotic complications after percutaneous coronary intervention (PCI). In-stent restenosis (ISR) is a complication that limits the long-term prognosis of PCI. The aim was to investigate the association between presence of the CYP2C19*2 allele and ISR within one-year after PCI in patients prescribed dual antiplatelet therapy with aspirin and clopidogrel. Methods Sixty patients with angiographically-confirmed drug eluting stent (DES)-ISR within 12 months post-PCI when on DAPT with aspirin and clopidogrel were retrospectively identified (Cases). Another 60 patients with no documented ISR post-PCI in the study period (Controls) were case-matched for age, gender, ethnicity, diabetes mellitus and estimated glomerular filtration rate value, and were invited for CYP2C19*2 genotyping. The association between presence of the CYP2C19*2 allele and ISR was analysed using the Fisher’s Exact test and binary logistic regression. Results Twenty-six (43.3%) cases and 5 (8.3%) controls were carriers of one or two CYP2C19*2 alleles. As to non-carrier status of the CYP2C19*2 allele, 34 (56.7%) cases and 55 (91.7%) controls were identified. The association between CYP2C19*2 carrier status and DES-ISR within one-year post-PCI was statistically significant (p<0.001) in both the univariate and multivariate analysis. Conclusions The proportion of patients who were carriers of one or two CYP2C19*2 alleles who presented with DES-ISR within one-year post-PCI while on clopidogrel was significantly higher compared to patients with no documented ISR.

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“…7,8 Clopidogrel is an inactive prodrug that requires liver activation by the cytochrome P450 enzyme complex, with CYP2C19 being one of the main enzymes involved in this process. 9 At least 34 allelic variants of human CYP2C19 have been defined by the Human CYP Allele Nomenclature Committee. Genetic polymorphisms in the CYP2C19 gene have been shown to contribute to alterations in enzyme activity.…”

Section: Introductionmentioning

confidence: 99%

<p>Impacts of <em>CYP2C19</em> Polymorphism and Clopidogrel Dosing on in-Stent Restenosis: A Retrospective Cohort Study in Chinese Patients</p>

Zhang

Wang

Zhang

et al. 2020

DDDT

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Objective: This retrospective cohort study is to analyze the impacts of CYP2C19 polymorphism and clopidogrel dosing on in-stent restenosis (ISR) after coronary stenting. Methods: Totally, 111 patients were included, who underwent percutaneous coronary intervention (PCI) with drug-eluting stent. Patients received clopidogrel treatment after the intervention on the background treatment with aspirin, based on the genotypes: 75 mg clopidogrel once each day for subjects without CYP2C19 loss-of-function (LOF) alleles (n=51; EM), 75 mg clopidogrel once each day (n=27; IM75) or twice each day (n=33; IM150) for subjects with one CYP2C19 LOF allele. ISR at 3-18 months after coronary stenting was assessed. Results: ISR rate was significantly higher in the IM75 group (40.7%) than the EM group (11.8%). ISR rate in the IM150 group was lower than the IM75 group (6.1% vs 40.7%), and comparable to that in the EM group. Multivariate logistic regression showed that both CYP2C19 genotype and clopidogrel dosing were associated with the risk of ISR after adjusting the relevant confounding factors. ISR risk was higher in the IM patients than the EM patients. Patients with clopidogrel dose of 75 mg once each day had significantly higher risk of ISR than those with the dose of 75 mg twice each day. Conclusion: Increased dose of clopidogrel may reduce the risk of ISR after PCI in CYP2C19 LOF allele(s) carriers. The presence of CYP2C19 LOF allele(s) increases the risk of ISR after stenting, which could be counteracted by the increased dose of clopidogrel.

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CYP2C19⁎2 Polymorphism in Chilean Patients with In-Stent Restenosis Development and Controls

Cited by 9 publications

References 43 publications

CYP2C19*2 Allele Carrier Status and Coronary In-stent Restenosis: Is There an Association?

CYP2C19*2 Allele Carrier Status and Coronary In-stent Restenosis: Is There an Association?

CYP2C192* genetic polymorphism and incidence of in-stent restenosis in patients on clopidogrel: a matched case-control study

<p>Impacts of <em>CYP2C19</em> Polymorphism and Clopidogrel Dosing on in-Stent Restenosis: A Retrospective Cohort Study in Chinese Patients</p>

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CYP2C19⁎2 Polymorphism in Chilean Patients with In-Stent Restenosis Development and Controls

Cited by 9 publications

References 43 publications

CYP2C19*2 Allele Carrier Status and Coronary In-stent Restenosis: Is There an Association?

CYP2C19*2 Allele Carrier Status and Coronary In-stent Restenosis: Is There an Association?

CYP2C19*2 genetic polymorphism and incidence of in-stent restenosis in patients on clopidogrel: a matched case-control study

<p>Impacts of <em>CYP2C19</em> Polymorphism and Clopidogrel Dosing on in-Stent Restenosis: A Retrospective Cohort Study in Chinese Patients</p>

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CYP2C192* genetic polymorphism and incidence of in-stent restenosis in patients on clopidogrel: a matched case-control study