Association of cytochrome P450 2C19*2 polymorphism with clopidogrel response variability and cardiovascular events in Koreans treated with drug-eluting stents

Oh, Il Young; Park, Kyung Woo; Kang, Si Hyuck; Park, Jin Joo; Na, Sang Hoon; Kang, Hyun Jae; Koo, Bon Kwon; Jeong, Young Hoon; Hwang, Jin Yong; Kwak, Choong Hwan; Park, Yongwhi; Hwang, Seok Jae; Ko, Young Guk; Shin, Dong Jik; Jang, Yangsoo; Kim, Hyo Soo

doi:10.1136/hrt.2011.227272

Cited by 73 publications

(46 citation statements)

References 26 publications

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“…The reduced-function CYP polymorphisms could influence the clopidogrel conversion from pro-drug to active metabolite, thus reducing the degree of platelet inhibition. Among the currently recognized CYP polymorphisms, the CYP2C19*2C genotype is associated with a diminished platelet response to clopidogrel and poor cardiovascular outcomes [5], especially in East Asians [32,33]. Because of a limited sample size, we did not observe difference in this genotype distribution in either PRI-determined or PAG-determined responders.…”

Section: Discussionmentioning

confidence: 60%

Decreased platelet miR-223 expression is associated with high on-clopidogrel platelet reactivity

Shi

Zhou

et al. 2013

Thrombosis Research

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Section: Discussionmentioning

confidence: 60%

Decreased platelet miR-223 expression is associated with high on-clopidogrel platelet reactivity

Shi

Zhou

et al. 2013

Thrombosis Research

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“…14, 15, 17, 18, 20–24 The effect of CYP polymorphisms on cardiovascular events among clopidogrel-treated patients after an acute coronary syndrome remains controversial, 25 and no studies to date have investigated the association of these CYP variants with outcomes in African American patients. In consideration of the Institute of Medicine’s recently articulated goal 26 to identify patient characteristics and treatments that vary by race in order to develop interventions that will minimize differences in care and eliminate disparities in outcomes, we investigated whether CYP variants were associated with different outcomes, including 1-year mortality, among clopidogrel-treated Caucasian and African American patients after AMI in the large, prospective, multicenter Translational Research Investigating Underlying disparities in acute Myocardial infarction Patients’ Health status (TRIUMPH) cohort.…”

Section: Introductionmentioning

confidence: 99%

Cytochrome P450 Gene Variants, Race, and Mortality Among Clopidogrel-Treated Patients After Acute Myocardial Infarction

Cresci

Depta

Lenzini

et al. 2014

Circ Cardiovasc Genet

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Background Clopidogrel is recommended after acute myocardial infarction (AMI) but has variable efficacy and safety, in part related to the effect of cytochrome P450 (CYP) polymorphisms on its metabolism. The effect of CYP polymorphisms on cardiovascular events among clopidogrel-treated patients after AMI remains controversial, and no studies to date have investigated the association of CYP variants with outcomes in African American patients. Methods and Results 2732 subjects (2062 Caucasians; 670 African Americans) hospitalized with AMI enrolled in the prospective, multicenter TRIUMPH study were genotyped for CYP polymorphisms. The majority of Caucasians (79%) and African Americans (64.4%) were discharged on clopidogrel. Among Caucasians, carriers of the loss-of-function CYP2C19*2 allele had significantly increased 1-year mortality (adjusted HR: 1.70; CI: 1.01 to 2.86; p=0.046), and a trend toward increased rate of recurrent MI (adjusted HR: 2.10; CI 0.95 to 4.63; p= 0.066). Among African Americans, increased 1-year mortality was associated with the gain of function CYP2C19*17 allele (adjusted HR for *1/*17 vs. *1/*1: 2.02; CI: 0.92 to 4.44; *17/*17 vs. *1/*1: 8.97; CI: 3.34 to 24.10; p< 0.0001) and the CYP1A2*1C allele (adjusted HR for *1/*1C vs. *1/*1: 1.89; CI: 0.85 to 4.22; *1C/*1C vs. *1/*1: 4.96; CI: 1.69 to 14.56; p= 0.014). Bleeding events were significantly more common among African American carriers of CYP2C19*17 or CYP1A2*1C. Conclusions Both loss of function and gain of function CYP polymorphisms affecting clopidogrel metabolism are associated with increased mortality among clopidogrel treated patients following AMI; the specific polymorphism and the putative mechanism vary according to race.

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“…Clopidogrel plays a significant role in the prevention of thrombotic events in patients undergoing PCI, but a substantial number of such events still occur [1], which can be partially explained by the phenomenon of drug resistance, up to 30% of patients in initial studies [2,3]. Oh et al [4] reported that the CYP2C19*2 allele carrier status was associated with an increased incidence of adverse clinical events.…”

Section: Introductionmentioning

confidence: 99%

Impact of cytochrome P450 2C19*2 polymorphism on the clinical cardiovascular events after stent implantation in patients receiving clopidogrel of a southern Tunisian region

Abid¹,

Laroussi²,

Bahloul³

et al. 2013

WJCD

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Introduction: The concept of clopidogrel resistance, first described in biology is being strengthened by recent data from clinical epidemiology. The cardiologists have been sensitized to this concept because of its possible involvement in the occurrence of coronary stent thrombosis. Purpose of the study: The purpose of this study was to investigate the genetic variant of the gene CYP 2C19 in our population and to assess the involvement of this genetic profile in the occurrence of major cardiovascular events (MACE) during the follow-up period. Methods: Our prospective study was conducted between May 2009 and September 2010 including 100 patients admitted to the cardiology department for percutaneous coronary stenting. The patients were divided into 2 groups: those with at least one CYP2C19*2 allele (*2 carriers) and noncarriers. Results: The mean age of our patients was 56.7 years ± 10, 5. No remarkable differences in the baseline characteristics were noted between the two groups. The prevalence of CYP2C19*2 allele in our population was 11.5%. Hospital mortality was estimated at 3%. No statistically significant differences were noted between the two groups regarding the occurrence of intra hospital MACE. The mean follow up was 7.5 ± 4.87 months for the entire study population. The rate of MACE during the follow-up of patients receiving clopidogrel was 8.2% throughout the study population: 5.3% in the *2 non-carriers versus 18.2% in the *2 carriers with a statistically significant difference (p = 0.075) at the risk of error of 10%. Concerning the occurrence of stent thrombosis, there was no significant statistical difference between the two study groups. Conclusion: From these results it is suggested that CYP2C19*2 polymorphism is associated with increase in the occurrence of MACE among Tunisian patients receiving clopidogrel. A larger study is needed to assess the role of genotyping in the evaluation of the phenomenon of clopidogrel resistance.

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Association of cytochrome P450 2C19*2 polymorphism with clopidogrel response variability and cardiovascular events in Koreans treated with drug-eluting stents

Abstract: The CYP2C19*2 genetic variant may be associated with worse outcome in Korean patients treated exclusively with DES and dual-antiplatelet therapy due to a significant increase in cardiac death, myocardial infarction or stent thrombosis.

Cited by 73 publications

References 26 publications

Decreased platelet miR-223 expression is associated with high on-clopidogrel platelet reactivity

Decreased platelet miR-223 expression is associated with high on-clopidogrel platelet reactivity

Cytochrome P450 Gene Variants, Race, and Mortality Among Clopidogrel-Treated Patients After Acute Myocardial Infarction

Impact of cytochrome P450 2C19*2 polymorphism on the clinical cardiovascular events after stent implantation in patients receiving clopidogrel of a southern Tunisian region

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