Clinical Impact of CYP2C19 Genotype on Clopidogrel-Based Antiplatelet Therapy After Percutaneous Coronary Intervention

PTRG-DES Registry Investigators

doi:10.1016/j.jcin.2023.01.363

Clinical Impact of CYP2C19 Genotype on Clopidogrel-Based Antiplatelet Therapy After Percutaneous Coronary Intervention

PTRG-DES Registry Investigators

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Although there is a growing body of evidence that CYP2C19 genotyping can be beneficial when considering treatment with clopidogrel after percutaneous coronary intervention (PCI), whether a genotype-guided strategy can be generally adopted in routine practice remains unclear among East Asians. Objectives: This study sought to investigate long-term outcomes of patients undergoing clopidogrel-based antiplatelet therapy after drug-eluting stent (DES) implantation according to CYP2C19 genotypes. Methods: From the nationwide multicenter PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) consortium, patients who underwent CYP2C19 genotyping were selected and classified according to CYP2C19 loss-of-function allele: rapid metabolizers (RMs) or normal metabolizers (NMs) vs intermediate metabolizers (IMs) or poor metabolizers (PMs). The primary outcome was a composite of cardiac death, myocardial infarction, and stent thrombosis at 5 years after the index procedure. Results: Of 8,163 patients with CYP2C19 genotyping, 56.7% presented with acute coronary syndrome. There were 3,098 (37.9%) in the RM or NM group, 3,906 (47.9%) in the IM group, and 1,159 (14.2%) in the PM group. IMs or PMs were associated with an increased risk of 5-year primary outcome compared with RMs or NMs (HR_adj: 1.42; 95% CI: 1.01-1.98; P = 0.041), and the effect was more pronounced in the first year (HR_adj: 1.67; 95% CI: 1.10-2.55; P = 0.016). The prognostic implication of being an IM and PM was significant in acute coronary syndrome patients (HR_adj: 1.88; 95% CI: 1.20-2.93; P = 0.005) but not in those with stable angina (HR_adj: 0.92; 95% CI: 0.54-1.55; P = 0.751) (interaction P = 0.028). Conclusions: Among East Asians with clopidogrel-based antiplatelet therapy after DES implantation, CYP2C19 genotyping could stratify patients who were likely to have an increased risk of atherothrombotic events.

Original language	English
Pages (from-to)	829-843
Number of pages	15
Journal	JACC: Cardiovascular Interventions
Volume	16
Issue number	7
DOIs	https://doi.org/10.1016/j.jcin.2023.01.363
Publication status	Published - 2023 Apr 10
Externally published	Yes

Keywords

CYP2C19 genotype
clopidogrel
drug-eluting stent(s)
percutaneous coronary intervention
prognosis

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jcin.2023.01.363

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@article{91b2c9e525d14c8a8aa9d21d9efc0c7f,

title = "Clinical Impact of CYP2C19 Genotype on Clopidogrel-Based Antiplatelet Therapy After Percutaneous Coronary Intervention",

abstract = "Background: Although there is a growing body of evidence that CYP2C19 genotyping can be beneficial when considering treatment with clopidogrel after percutaneous coronary intervention (PCI), whether a genotype-guided strategy can be generally adopted in routine practice remains unclear among East Asians. Objectives: This study sought to investigate long-term outcomes of patients undergoing clopidogrel-based antiplatelet therapy after drug-eluting stent (DES) implantation according to CYP2C19 genotypes. Methods: From the nationwide multicenter PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) consortium, patients who underwent CYP2C19 genotyping were selected and classified according to CYP2C19 loss-of-function allele: rapid metabolizers (RMs) or normal metabolizers (NMs) vs intermediate metabolizers (IMs) or poor metabolizers (PMs). The primary outcome was a composite of cardiac death, myocardial infarction, and stent thrombosis at 5 years after the index procedure. Results: Of 8,163 patients with CYP2C19 genotyping, 56.7% presented with acute coronary syndrome. There were 3,098 (37.9%) in the RM or NM group, 3,906 (47.9%) in the IM group, and 1,159 (14.2%) in the PM group. IMs or PMs were associated with an increased risk of 5-year primary outcome compared with RMs or NMs (HRadj: 1.42; 95% CI: 1.01-1.98; P = 0.041), and the effect was more pronounced in the first year (HRadj: 1.67; 95% CI: 1.10-2.55; P = 0.016). The prognostic implication of being an IM and PM was significant in acute coronary syndrome patients (HRadj: 1.88; 95% CI: 1.20-2.93; P = 0.005) but not in those with stable angina (HRadj: 0.92; 95% CI: 0.54-1.55; P = 0.751) (interaction P = 0.028). Conclusions: Among East Asians with clopidogrel-based antiplatelet therapy after DES implantation, CYP2C19 genotyping could stratify patients who were likely to have an increased risk of atherothrombotic events.",

keywords = "CYP2C19 genotype, clopidogrel, drug-eluting stent(s), percutaneous coronary intervention, prognosis",

author = "{PTRG-DES Registry Investigators} and Lee, {Seung Hun} and Jeong, {Young Hoon} and David Hong and Choi, {Ki Hong} and Lee, {Joo Myung} and Park, {Taek Kyu} and Yang, {Jeong Hoon} and Hahn, {Joo Yong} and Choi, {Seung Hyuck} and Gwon, {Hyeon Cheol} and Jeong, {Myung Ho} and Kim, {Byeong Keuk} and Joo, {Hyung Joon} and Kiyuk Chang and Yongwhi Park and Ahn, {Sung Gyun} and Suh, {Jung Won} and Lee, {Sang Yeub} and Cho, {Jung Rae} and Her, {Ae Young} and Kim, {Hyo Soo} and Kim, {Moo Hyun} and Lim, {Do Sun} and Shin, {Eun Seok} and Song, {Young Bin}",

note = "Publisher Copyright: {\textcopyright} 2023 American College of Cardiology Foundation",

year = "2023",

month = apr,

day = "10",

doi = "10.1016/j.jcin.2023.01.363",

language = "English",

volume = "16",

pages = "829--843",

journal = "JACC: Cardiovascular Interventions",

issn = "1936-8798",

publisher = "Elsevier Inc.",

number = "7",

}

TY - JOUR

T1 - Clinical Impact of CYP2C19 Genotype on Clopidogrel-Based Antiplatelet Therapy After Percutaneous Coronary Intervention

AU - PTRG-DES Registry Investigators

AU - Lee, Seung Hun

AU - Jeong, Young Hoon

AU - Hong, David

AU - Choi, Ki Hong

AU - Lee, Joo Myung

AU - Park, Taek Kyu

AU - Yang, Jeong Hoon

AU - Hahn, Joo Yong

AU - Choi, Seung Hyuck

AU - Gwon, Hyeon Cheol

AU - Jeong, Myung Ho

AU - Kim, Byeong Keuk

AU - Joo, Hyung Joon

AU - Chang, Kiyuk

AU - Park, Yongwhi

AU - Ahn, Sung Gyun

AU - Suh, Jung Won

AU - Lee, Sang Yeub

AU - Cho, Jung Rae

AU - Her, Ae Young

AU - Kim, Hyo Soo

AU - Kim, Moo Hyun

AU - Lim, Do Sun

AU - Shin, Eun Seok

AU - Song, Young Bin

PY - 2023/4/10

Y1 - 2023/4/10

N2 - Background: Although there is a growing body of evidence that CYP2C19 genotyping can be beneficial when considering treatment with clopidogrel after percutaneous coronary intervention (PCI), whether a genotype-guided strategy can be generally adopted in routine practice remains unclear among East Asians. Objectives: This study sought to investigate long-term outcomes of patients undergoing clopidogrel-based antiplatelet therapy after drug-eluting stent (DES) implantation according to CYP2C19 genotypes. Methods: From the nationwide multicenter PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) consortium, patients who underwent CYP2C19 genotyping were selected and classified according to CYP2C19 loss-of-function allele: rapid metabolizers (RMs) or normal metabolizers (NMs) vs intermediate metabolizers (IMs) or poor metabolizers (PMs). The primary outcome was a composite of cardiac death, myocardial infarction, and stent thrombosis at 5 years after the index procedure. Results: Of 8,163 patients with CYP2C19 genotyping, 56.7% presented with acute coronary syndrome. There were 3,098 (37.9%) in the RM or NM group, 3,906 (47.9%) in the IM group, and 1,159 (14.2%) in the PM group. IMs or PMs were associated with an increased risk of 5-year primary outcome compared with RMs or NMs (HRadj: 1.42; 95% CI: 1.01-1.98; P = 0.041), and the effect was more pronounced in the first year (HRadj: 1.67; 95% CI: 1.10-2.55; P = 0.016). The prognostic implication of being an IM and PM was significant in acute coronary syndrome patients (HRadj: 1.88; 95% CI: 1.20-2.93; P = 0.005) but not in those with stable angina (HRadj: 0.92; 95% CI: 0.54-1.55; P = 0.751) (interaction P = 0.028). Conclusions: Among East Asians with clopidogrel-based antiplatelet therapy after DES implantation, CYP2C19 genotyping could stratify patients who were likely to have an increased risk of atherothrombotic events.

AB - Background: Although there is a growing body of evidence that CYP2C19 genotyping can be beneficial when considering treatment with clopidogrel after percutaneous coronary intervention (PCI), whether a genotype-guided strategy can be generally adopted in routine practice remains unclear among East Asians. Objectives: This study sought to investigate long-term outcomes of patients undergoing clopidogrel-based antiplatelet therapy after drug-eluting stent (DES) implantation according to CYP2C19 genotypes. Methods: From the nationwide multicenter PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) consortium, patients who underwent CYP2C19 genotyping were selected and classified according to CYP2C19 loss-of-function allele: rapid metabolizers (RMs) or normal metabolizers (NMs) vs intermediate metabolizers (IMs) or poor metabolizers (PMs). The primary outcome was a composite of cardiac death, myocardial infarction, and stent thrombosis at 5 years after the index procedure. Results: Of 8,163 patients with CYP2C19 genotyping, 56.7% presented with acute coronary syndrome. There were 3,098 (37.9%) in the RM or NM group, 3,906 (47.9%) in the IM group, and 1,159 (14.2%) in the PM group. IMs or PMs were associated with an increased risk of 5-year primary outcome compared with RMs or NMs (HRadj: 1.42; 95% CI: 1.01-1.98; P = 0.041), and the effect was more pronounced in the first year (HRadj: 1.67; 95% CI: 1.10-2.55; P = 0.016). The prognostic implication of being an IM and PM was significant in acute coronary syndrome patients (HRadj: 1.88; 95% CI: 1.20-2.93; P = 0.005) but not in those with stable angina (HRadj: 0.92; 95% CI: 0.54-1.55; P = 0.751) (interaction P = 0.028). Conclusions: Among East Asians with clopidogrel-based antiplatelet therapy after DES implantation, CYP2C19 genotyping could stratify patients who were likely to have an increased risk of atherothrombotic events.

KW - CYP2C19 genotype

KW - clopidogrel

KW - drug-eluting stent(s)

KW - percutaneous coronary intervention

KW - prognosis

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U2 - 10.1016/j.jcin.2023.01.363

DO - 10.1016/j.jcin.2023.01.363

M3 - Article

C2 - 37045504

AN - SCOPUS:85151402455

SN - 1936-8798

VL - 16

SP - 829

EP - 843

JO - JACC: Cardiovascular Interventions

JF - JACC: Cardiovascular Interventions

IS - 7

ER -

Clinical Impact of CYP2C19 Genotype on Clopidogrel-Based Antiplatelet Therapy After Percutaneous Coronary Intervention

Abstract

Keywords

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