Abstract
Rationale: The P2Y12 receptor inhibitor clopidogrel is widely used in patients with acute coronary syndrome, percutaneous coronary intervention, or ischemic stroke. Platelet inhibition by clopidogrel shows wide interpatient variability, and high on-treatment platelet reactivity is a risk factor for atherothrombotic events, particularly in high-risk populations. CYP2C19 polymorphism plays an important role in this variability, but heritability estimates suggest that additional genetic variants remain unidentified. The aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify genetic determinants of clopidogrel pharmacodynamics and clinical response. Study design: Based on the data published on www.clinicaltrials.gov, clopidogrel intervention studies containing genetic and platelet function data were identified for participation. Lead investigators were invited to share DNA samples, platelet function test results, patient characteristics, and cardiovascular outcomes to perform candidate gene and genome-wide studies. Results: In total, 17 study sites from 13 countries participate in the ICPC, contributing individual patient data from 8,829 patients. Available adenosine diphosphate–stimulated platelet function tests included vasodilator-stimulated phosphoprotein assay, light transmittance aggregometry, and the VerifyNow P2Y12 assay. A proof-of-principle analysis based on genotype data provided by each group showed a strong and consistent association between CYP2C19*2 and platelet reactivity (P value = 5.1 × 10−40). Conclusion: The ICPC aims to identify new loci influencing clopidogrel efficacy by using state-of-the-art genetic approaches in a large cohort of clopidogrel-treated patients to better understand the genetic basis of on-treatment response variability.
| Original language | English |
|---|---|
| Pages (from-to) | 152-159 |
| Number of pages | 8 |
| Journal | American Heart Journal |
| Volume | 198 |
| DOIs | |
| Publication status | Published - 04-2018 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine
Cite this
}
Genome-wide and candidate gene approaches of clopidogrel efficacy using pharmacodynamic and clinical end points—Rationale and design of the International Clopidogrel Pharmacogenomics Consortium (ICPC). / for the ICPC Investigators.
In: American Heart Journal, Vol. 198, 04.2018, p. 152-159.Research output: Contribution to journal › Article
TY - JOUR
T1 - Genome-wide and candidate gene approaches of clopidogrel efficacy using pharmacodynamic and clinical end points—Rationale and design of the International Clopidogrel Pharmacogenomics Consortium (ICPC)
AU - for the ICPC Investigators
AU - Bergmeijer, Thomas O.
AU - Reny, Jean Luc
AU - Pakyz, Ruth E.
AU - Gong, Li
AU - Lewis, Joshua P.
AU - Kim, Eun Young
AU - Aradi, Daniel
AU - Fernandez-Cadenas, Israel
AU - Horenstein, Richard B.
AU - Lee, Ming Ta Michael
AU - Whaley, Ryan M.
AU - Montaner, Joan
AU - Gensini, Gian Franco
AU - Cleator, John H.
AU - Chang, Kiyuk
AU - Holmvang, Lene
AU - Hochholzer, Willibald
AU - Roden, Dan M.
AU - Winter, Stefan
AU - Altman, Russ B.
AU - Alexopoulos, Dimitrios
AU - Kim, Ho Sook
AU - Déry, Jean Pierre
AU - Gawaz, Meinrad
AU - Bliden, Kevin
AU - Valgimigli, Marco
AU - Marcucci, Rossella
AU - Campo, Gianluca
AU - Schaeffeler, Elke
AU - Dridi, Nadia P.
AU - Wen, Ming Shien
AU - Shin, Jae Gook
AU - Simon, Tabassome
AU - Fontana, Pierre
AU - Giusti, Betti
AU - Geisler, Tobias
AU - Kubo, Michiaki
AU - Trenk, Dietmar
AU - Siller-Matula, Jolanta M.
AU - ten Berg, Jurriën M.
AU - Gurbel, Paul A.
AU - Hulot, Jean Sebastien
AU - Mitchell, Braxton D.
AU - Schwab, Matthias
AU - Ritchie, Marylyn De Riggi
AU - Klein, Teri E.
AU - Shuldiner, Alan R.
PY - 2018/4
Y1 - 2018/4
N2 - Rationale: The P2Y12 receptor inhibitor clopidogrel is widely used in patients with acute coronary syndrome, percutaneous coronary intervention, or ischemic stroke. Platelet inhibition by clopidogrel shows wide interpatient variability, and high on-treatment platelet reactivity is a risk factor for atherothrombotic events, particularly in high-risk populations. CYP2C19 polymorphism plays an important role in this variability, but heritability estimates suggest that additional genetic variants remain unidentified. The aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify genetic determinants of clopidogrel pharmacodynamics and clinical response. Study design: Based on the data published on www.clinicaltrials.gov, clopidogrel intervention studies containing genetic and platelet function data were identified for participation. Lead investigators were invited to share DNA samples, platelet function test results, patient characteristics, and cardiovascular outcomes to perform candidate gene and genome-wide studies. Results: In total, 17 study sites from 13 countries participate in the ICPC, contributing individual patient data from 8,829 patients. Available adenosine diphosphate–stimulated platelet function tests included vasodilator-stimulated phosphoprotein assay, light transmittance aggregometry, and the VerifyNow P2Y12 assay. A proof-of-principle analysis based on genotype data provided by each group showed a strong and consistent association between CYP2C19*2 and platelet reactivity (P value = 5.1 × 10−40). Conclusion: The ICPC aims to identify new loci influencing clopidogrel efficacy by using state-of-the-art genetic approaches in a large cohort of clopidogrel-treated patients to better understand the genetic basis of on-treatment response variability.
AB - Rationale: The P2Y12 receptor inhibitor clopidogrel is widely used in patients with acute coronary syndrome, percutaneous coronary intervention, or ischemic stroke. Platelet inhibition by clopidogrel shows wide interpatient variability, and high on-treatment platelet reactivity is a risk factor for atherothrombotic events, particularly in high-risk populations. CYP2C19 polymorphism plays an important role in this variability, but heritability estimates suggest that additional genetic variants remain unidentified. The aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify genetic determinants of clopidogrel pharmacodynamics and clinical response. Study design: Based on the data published on www.clinicaltrials.gov, clopidogrel intervention studies containing genetic and platelet function data were identified for participation. Lead investigators were invited to share DNA samples, platelet function test results, patient characteristics, and cardiovascular outcomes to perform candidate gene and genome-wide studies. Results: In total, 17 study sites from 13 countries participate in the ICPC, contributing individual patient data from 8,829 patients. Available adenosine diphosphate–stimulated platelet function tests included vasodilator-stimulated phosphoprotein assay, light transmittance aggregometry, and the VerifyNow P2Y12 assay. A proof-of-principle analysis based on genotype data provided by each group showed a strong and consistent association between CYP2C19*2 and platelet reactivity (P value = 5.1 × 10−40). Conclusion: The ICPC aims to identify new loci influencing clopidogrel efficacy by using state-of-the-art genetic approaches in a large cohort of clopidogrel-treated patients to better understand the genetic basis of on-treatment response variability.
UR - http://www.scopus.com/inward/record.url?scp=85040931385&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040931385&partnerID=8YFLogxK
U2 - 10.1016/j.ahj.2017.12.010
DO - 10.1016/j.ahj.2017.12.010
M3 - Article
C2 - 29653637
AN - SCOPUS:85040931385
VL - 198
SP - 152
EP - 159
JO - American Heart Journal
JF - American Heart Journal
SN - 0002-8703
ER -