Effects of genetic variants on platelet reactivity and one-year clinical outcomes after percutaneous coronary intervention

A prospective multicentre registry study

Hyung Joon Joo, Sung Gyun Ahn, Jae Hyoung Park, Ji-Young Park, Soon Jun Hong, Seok Yeon Kim, Woong Gil Choi, Hyeon Cheol Gwon, Young Hyo Lim, Weon Kim, Woong Chol Kang, Yun Hyeong Cho, Yong Hoon Kim, Jung Han Yoon, Won Yong Shin, Myeong Ki Hong, Scot Garg, Yangsoo Jang, Do-Sun Lim

Research output: Contribution to journalArticle

4 Citations (Scopus)

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, p = 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.

Original languageEnglish
Article number1229
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

Fingerprint

Percutaneous Coronary Intervention
Multicenter Studies
Registries
Blood Platelets
Drug-Eluting Stents
clopidogrel
Stents
Thrombosis
Therapeutics
Myocardial Infarction
Hemorrhage
Genetic Polymorphisms
Platelet Count
Proportional Hazards Models
Single Nucleotide Polymorphism
Stroke
Alleles
Confidence Intervals
Incidence
Cytochrome P-450 CYP2C19

ASJC Scopus subject areas

  • General

Cite this

Effects of genetic variants on platelet reactivity and one-year clinical outcomes after percutaneous coronary intervention : A prospective multicentre registry study. / Joo, Hyung Joon; Ahn, Sung Gyun; Park, Jae Hyoung; Park, Ji-Young; Hong, Soon Jun; Kim, Seok Yeon; Choi, Woong Gil; Gwon, Hyeon Cheol; Lim, Young Hyo; Kim, Weon; Kang, Woong Chol; Cho, Yun Hyeong; Kim, Yong Hoon; Yoon, Jung Han; Shin, Won Yong; Hong, Myeong Ki; Garg, Scot; Jang, Yangsoo; Lim, Do-Sun.

In: Scientific Reports, Vol. 8, No. 1, 1229, 01.12.2018.

Research output: Contribution to journalArticle

Joo, Hyung Joon ; Ahn, Sung Gyun ; Park, Jae Hyoung ; Park, Ji-Young ; Hong, Soon Jun ; Kim, Seok Yeon ; Choi, Woong Gil ; Gwon, Hyeon Cheol ; Lim, Young Hyo ; Kim, Weon ; Kang, Woong Chol ; Cho, Yun Hyeong ; Kim, Yong Hoon ; Yoon, Jung Han ; Shin, Won Yong ; Hong, Myeong Ki ; Garg, Scot ; Jang, Yangsoo ; Lim, Do-Sun. / Effects of genetic variants on platelet reactivity and one-year clinical outcomes after percutaneous coronary intervention : A prospective multicentre registry study. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
@article{37e642b1ce9c49e49306eaa0b2e87bc9,
title = "Effects of genetic variants on platelet reactivity and one-year clinical outcomes after percutaneous coronary intervention: A prospective multicentre registry study",
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, p = 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.",
author = "Joo, {Hyung Joon} and Ahn, {Sung Gyun} and Park, {Jae Hyoung} and Ji-Young Park and Hong, {Soon Jun} and Kim, {Seok Yeon} and Choi, {Woong Gil} and Gwon, {Hyeon Cheol} and Lim, {Young Hyo} and Weon Kim and Kang, {Woong Chol} and Cho, {Yun Hyeong} and Kim, {Yong Hoon} and Yoon, {Jung Han} and Shin, {Won Yong} and Hong, {Myeong Ki} and Scot Garg and Yangsoo Jang and Do-Sun Lim",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41598-017-18134-y",
language = "English",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Effects of genetic variants on platelet reactivity and one-year clinical outcomes after percutaneous coronary intervention

T2 - A prospective multicentre registry study

AU - Joo, Hyung Joon

AU - Ahn, Sung Gyun

AU - Park, Jae Hyoung

AU - Park, Ji-Young

AU - Hong, Soon Jun

AU - Kim, Seok Yeon

AU - Choi, Woong Gil

AU - Gwon, Hyeon Cheol

AU - Lim, Young Hyo

AU - Kim, Weon

AU - Kang, Woong Chol

AU - Cho, Yun Hyeong

AU - Kim, Yong Hoon

AU - Yoon, Jung Han

AU - Shin, Won Yong

AU - Hong, Myeong Ki

AU - Garg, Scot

AU - Jang, Yangsoo

AU - Lim, Do-Sun

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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, p = 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.

AB - 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, p = 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.

UR - http://www.scopus.com/inward/record.url?scp=85040830638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040830638&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-18134-y

DO - 10.1038/s41598-017-18134-y

M3 - Article

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 1229

ER -