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)

Am Heart J. 2018 Apr;198:152-159. doi: 10.1016/j.ahj.2017.12.010. Epub 2017 Dec 17.


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, 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.

Trial registration: NCT00799396.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute Coronary Syndrome / diagnosis
  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / mortality
  • Aged
  • Clopidogrel / therapeutic use*
  • Female
  • Genetic Association Studies
  • Genome-Wide Association Study*
  • Humans
  • Internationality
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods*
  • Pharmacogenetics
  • Prognosis
  • Receptors, Purinergic P2Y12 / drug effects
  • Receptors, Purinergic P2Y12 / genetics*
  • Risk Assessment
  • Survival Rate
  • Treatment Outcome


  • P2RY12 protein, human
  • Receptors, Purinergic P2Y12
  • Clopidogrel

Associated data