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Sci Rep. 2018 Jan 19;8(1):1229. doi: 10.1038/s41598-017-18134-y.

Effects of genetic variants on platelet reactivity and one-year clinical outcomes after percutaneous coronary intervention: A prospective multicentre registry study.

Author information

1
Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, South Korea.
2
Department of Cardiology, Yonsei University Wonju Severance Christian Hospital, Wonju, South Korea.
3
Department of Clinical Pharmacology and Toxicology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea.
4
Department of Cardiology, Seoul Medical Center, Seoul, South Korea.
5
Division of Cardiology, Department of Internal Medicine, Konkuk University College of Medicine, Chungju, South Korea.
6
Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
7
Division of Cardiology, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea.
8
Department of Internal Medicine, Division of Cardiology, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul, South Korea.
9
Department of Cardiology, Gachon University Gil Medical Center, Incheon, South Korea.
10
Department of Internal Medicine, Seonam University Myongji Hospital, Goyang, South Korea.
11
Division of Cardiology, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon City, South Korea.
12
Division of Cardiology, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, South Korea.
13
Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea.
14
East Lancashire Hospitals NHS Trust, Blackburn, Lancashire, UK.
15
Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea. jangys1212@yuhs.or.kr.
16
Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, South Korea. dslmd@kumc.or.kr.

Abstract

Clopidogrel is the mainstay for antiplatelet treatment after percutaneous coronary intervention (PCI). The relationship of platelet reactivity and genetic polymorphism with clinical outcomes with newer-generation drug-eluting stents is unclear. We analysed 4,587 patients for the most powerful single-nucleotide polymorphisms (CYP2C19, CYP2C9, ABCB1, PON1, and P2Y12) related to on-treatment platelet reactivity (OPR). The optimal cut-off value of high OPR for major adverse thrombotic events was 266. CYP2C19 was significantly associated with high OPR and the number of CYP2C19*R (*2 or *3) alleles was proportional to the increased risk of high OPR. Death, myocardial infarction (MI), stroke, stent thrombosis, and bleeding events were assessed during a 1-year follow-up period. Primary endpoints were death and non-fatal MI. The cumulative 1-year incidence of death and stent thrombosis was significantly higher in patients with CYP2C19*2/*2, CYP2C19*2/*3, and CYP2C19*3/*3 (Group 3) than in patients with CYP2C19*1/*1 (Group 1). Multivariate Cox proportional hazard model showed that cardiac death risk was significantly higher in Group 3 than in Group 1 (hazard ratio 2.69, 95% confidence interval 1.154-6.263, pā€‰=ā€‰0.022). No association was reported between bleeding and OPR. Thus, CYP2C19 may exert a significant impact on the prognosis of PCI patients even in the era of newer-generation drug-eluting stents.

PMID:
29352151
PMCID:
PMC5775197
DOI:
10.1038/s41598-017-18134-y
[Indexed for MEDLINE]
Free PMC Article

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