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

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

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Abstract

Background: Although East Asians carry the cytochrome P450 (CYP) 2C19*2 allele more frequently than do Caucasians, the impact of the CYP2C19*2 allele on clopidogrel pharmacodynamics and clinical outcomes is unknown. Objective: To evaluate the effect of CYP2C19 variants on clopidogrel pharmacodynamics and long-term prognosis in East Asian patients with drug-eluting stents (DES). Methods: DES-treated patients taking dual antiplatelet therapy were enrolled from a Korean multicentre genetic registry. The CYP2C19*2 allele was genotyped using the Taqman method (n=2146), and on-treatment platelet reactivity was measured with the VerifyNow P2Y12 assay (n=1415). Results: 1011 patients (47%) carried at least one CYP2C19*2 allele. The mean on-treatment platelet reactivity was significantly higher in carriers than in non-carriers (250±76 vs 231±83 P2Y12 reaction unit, p<0.001). For up to 12 months' follow-up, the composite of cardiovascular death, non-fatal myocardial infarction and stent thrombosis was significantly higher in carriers of the CYP2C19*2 allele than non-carriers (2.0% vs 0.8%, p=0.02). On landmark analysis, there was no difference in clinical outcome after 12 months between the groups. Conclusion: 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.

Original languageEnglish
Pages (from-to)139-144
Number of pages6
JournalHeart
Volume98
Issue number2
DOIs
Publication statusPublished - 2012 Jan 1

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clopidogrel
Drug-Eluting Stents
Cytochrome P-450 Enzyme System
Alleles
Stents
Thrombosis
Blood Platelets
Myocardial Infarction
Therapeutics
Registries
Cytochrome P-450 CYP2C19

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Oh, Il Young ; Park, Kyung Woo ; Kang, Si Hyuk ; 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. / Association of cytochrome P450 2C19*2 polymorphism with clopidogrel response variability and cardiovascular events in Koreans treated with drug-eluting stents. In: Heart. 2012 ; Vol. 98, No. 2. pp. 139-144.
@article{dd5a8d71bd634b52acf4375813372deb,
title = "Association of cytochrome P450 2C19*2 polymorphism with clopidogrel response variability and cardiovascular events in Koreans treated with drug-eluting stents",
abstract = "Background: Although East Asians carry the cytochrome P450 (CYP) 2C19*2 allele more frequently than do Caucasians, the impact of the CYP2C19*2 allele on clopidogrel pharmacodynamics and clinical outcomes is unknown. Objective: To evaluate the effect of CYP2C19 variants on clopidogrel pharmacodynamics and long-term prognosis in East Asian patients with drug-eluting stents (DES). Methods: DES-treated patients taking dual antiplatelet therapy were enrolled from a Korean multicentre genetic registry. The CYP2C19*2 allele was genotyped using the Taqman method (n=2146), and on-treatment platelet reactivity was measured with the VerifyNow P2Y12 assay (n=1415). Results: 1011 patients (47{\%}) carried at least one CYP2C19*2 allele. The mean on-treatment platelet reactivity was significantly higher in carriers than in non-carriers (250±76 vs 231±83 P2Y12 reaction unit, p<0.001). For up to 12 months' follow-up, the composite of cardiovascular death, non-fatal myocardial infarction and stent thrombosis was significantly higher in carriers of the CYP2C19*2 allele than non-carriers (2.0{\%} vs 0.8{\%}, p=0.02). On landmark analysis, there was no difference in clinical outcome after 12 months between the groups. Conclusion: 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.",
author = "Oh, {Il Young} and Park, {Kyung Woo} and Kang, {Si Hyuk} and Park, {Jin Joo} and Na, {Sang Hoon} and Kang, {Hyun Jae} and Koo, {Bon Kwon} and Jeong, {Young Hoon} and Hwang, {Jin Yong} and Kwak, {Choong Hwan} and Yongwhi Park and Hwang, {Seok Jae} and Ko, {Young Guk} and Shin, {Dong Jik} and Yangsoo Jang and Kim, {Hyo Soo}",
year = "2012",
month = "1",
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doi = "10.1136/hrt.2011.227272",
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Oh, IY, Park, KW, Kang, SH, Park, JJ, Na, SH, Kang, HJ, Koo, BK, Jeong, YH, Hwang, JY, Kwak, CH, Park, Y, Hwang, SJ, Ko, YG, Shin, DJ, Jang, Y & Kim, HS 2012, 'Association of cytochrome P450 2C19*2 polymorphism with clopidogrel response variability and cardiovascular events in Koreans treated with drug-eluting stents', Heart, vol. 98, no. 2, pp. 139-144. https://doi.org/10.1136/hrt.2011.227272

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 Hyuk; 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.

In: Heart, Vol. 98, No. 2, 01.01.2012, p. 139-144.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association of cytochrome P450 2C19*2 polymorphism with clopidogrel response variability and cardiovascular events in Koreans treated with drug-eluting stents

AU - Oh, Il Young

AU - Park, Kyung Woo

AU - Kang, Si Hyuk

AU - Park, Jin Joo

AU - Na, Sang Hoon

AU - Kang, Hyun Jae

AU - Koo, Bon Kwon

AU - Jeong, Young Hoon

AU - Hwang, Jin Yong

AU - Kwak, Choong Hwan

AU - Park, Yongwhi

AU - Hwang, Seok Jae

AU - Ko, Young Guk

AU - Shin, Dong Jik

AU - Jang, Yangsoo

AU - Kim, Hyo Soo

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Background: Although East Asians carry the cytochrome P450 (CYP) 2C19*2 allele more frequently than do Caucasians, the impact of the CYP2C19*2 allele on clopidogrel pharmacodynamics and clinical outcomes is unknown. Objective: To evaluate the effect of CYP2C19 variants on clopidogrel pharmacodynamics and long-term prognosis in East Asian patients with drug-eluting stents (DES). Methods: DES-treated patients taking dual antiplatelet therapy were enrolled from a Korean multicentre genetic registry. The CYP2C19*2 allele was genotyped using the Taqman method (n=2146), and on-treatment platelet reactivity was measured with the VerifyNow P2Y12 assay (n=1415). Results: 1011 patients (47%) carried at least one CYP2C19*2 allele. The mean on-treatment platelet reactivity was significantly higher in carriers than in non-carriers (250±76 vs 231±83 P2Y12 reaction unit, p<0.001). For up to 12 months' follow-up, the composite of cardiovascular death, non-fatal myocardial infarction and stent thrombosis was significantly higher in carriers of the CYP2C19*2 allele than non-carriers (2.0% vs 0.8%, p=0.02). On landmark analysis, there was no difference in clinical outcome after 12 months between the groups. Conclusion: 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.

AB - Background: Although East Asians carry the cytochrome P450 (CYP) 2C19*2 allele more frequently than do Caucasians, the impact of the CYP2C19*2 allele on clopidogrel pharmacodynamics and clinical outcomes is unknown. Objective: To evaluate the effect of CYP2C19 variants on clopidogrel pharmacodynamics and long-term prognosis in East Asian patients with drug-eluting stents (DES). Methods: DES-treated patients taking dual antiplatelet therapy were enrolled from a Korean multicentre genetic registry. The CYP2C19*2 allele was genotyped using the Taqman method (n=2146), and on-treatment platelet reactivity was measured with the VerifyNow P2Y12 assay (n=1415). Results: 1011 patients (47%) carried at least one CYP2C19*2 allele. The mean on-treatment platelet reactivity was significantly higher in carriers than in non-carriers (250±76 vs 231±83 P2Y12 reaction unit, p<0.001). For up to 12 months' follow-up, the composite of cardiovascular death, non-fatal myocardial infarction and stent thrombosis was significantly higher in carriers of the CYP2C19*2 allele than non-carriers (2.0% vs 0.8%, p=0.02). On landmark analysis, there was no difference in clinical outcome after 12 months between the groups. Conclusion: 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.

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U2 - 10.1136/hrt.2011.227272

DO - 10.1136/hrt.2011.227272

M3 - Article

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SP - 139

EP - 144

JO - Heart

JF - Heart

SN - 1355-6037

IS - 2

ER -