Association of cytochrome P450 2C19*2 polymorphism with clopidogrel response variability and cardiovascular events in Koreans treated with drug-eluting stents
- Il-Young Oh1,2,
- Kyung Woo Park1,
- Si-Hyuk Kang1,
- Jin Joo Park1,
- Sang-Hoon Na1,
- Hyun-Jae Kang1,
- Bon-Kwon Koo1,
- Young-Hoon Jeong3,
- Jin-Yong Hwang3,
- Choong Hwan Kwak3,
- Yongwhi Park3,
- Seok-Jae Hwang3,
- Young-Guk Ko4,
- Dong Jik Shin4,
- Yangsoo Jang4,
- Hyo-Soo Kim1
- 1Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul, Korea
- 2Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam, Korea
- 3Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea
- 4Division of Cardiology and Cardiovascular Genome Center, Severance Cardiovascular Hospital, Yonsei University Health System, Seoul, Korea
- Correspondence to Dr Hyo-Soo Kim, Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, 28 Yongong-dong, Chongno-gu, Seoul 110-744, Korea;
- Accepted 24 May 2011
- Published Online First 23 June 2011
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.
Linked article 227652.
Il-Young Oh and Kyung Woo Park contributed equally to this study.
Funding This study was supported by grants from the Korean Society of Interventional Cardiology (2010), from the Clinical Research Center for Ischemic Heart Disease (A040152), and from the Innovative Research Institute for Cell Therapy, Seoul National University Hospital (A062260), sponsored by the Ministry of Health, Welfare & Family, Korea. Dr. Hyo-Soo Kim is also a professor of Word Class University Program, Molecular Medicine and Biopharmaceutical Sciences, Seoul National University sponsored by the Ministry of Education, Science & Technology, Korea.
Competing interests None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the Seoul National University Hospital Institutes for Biomedical Research.
Provenance and peer review Not commissioned; externally peer reviewed.