Clopidogrel pharmacogenetics state-of-the-art review and the TAILOR-PCI study

Naveen L. Pereira, Charanjit S. Rihal, Derek Y.F. So, Yves Rosenberg, Ryan J. Lennon, Verghese Mathew, Shaun G. Goodman, Richard M. Weinshilboum, Liewei Wang, Linnea M. Baudhuin, Amir Lerman, Ahmed Hasan, Erin Iturriaga, Yi Ping Fu, Nancy Geller, Kent Bailey, Michael E. Farkouh

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Common genetic variation in CYP2C19 (cytochrome P450, family 2, subfamily C, polypeptide 19) *2 and *3 alleles leads to a loss of functional protein, and carriers of these loss-of-function alleles when treated with clopidogrel have significantly reduced clopidogrel active metabolite levels and high on-treatment platelet reactivity resulting in increased risk of major adverse cardiovascular events, especially after percutaneous coronary intervention. The Food and Drug Administration has issued a black box warning advising practitioners to consider alternative treatment in CYP2C19 poor metabolizers who might receive clopidogrel and to identify such patients by genotyping. However, routine clinical use of genotyping for CYP2C19 loss-of-function alleles in patients undergoing percutaneous coronary intervention is not recommended by clinical guidelines because of lack of prospective evidence. To address this critical gap, TAILOR-PCI (Tailored Antiplatelet Initiation to Lessen Outcomes due to Decreased Clopidogrel Response After Percutaneous Coronary Intervention) is a large, pragmatic, randomized trial comparing point-of-care genotype-guided antiplatelet therapy with routine care to determine whether identifying CYP2C19 loss-of-function allele patients prospectively and prescribing alternative antiplatelet therapy is beneficial.

Original languageEnglish (US)
JournalCirculation: Cardiovascular Interventions
Volume12
Issue number4
DOIs
StatePublished - Apr 1 2019

Keywords

  • Clinical trial
  • Clopidogrel
  • Cytochrome P450 CYP2C19
  • Drug labeling
  • Genetics
  • Humans
  • Pharmacogenetics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Clopidogrel pharmacogenetics state-of-the-art review and the TAILOR-PCI study'. Together they form a unique fingerprint.

  • Cite this

    Pereira, N. L., Rihal, C. S., So, D. Y. F., Rosenberg, Y., Lennon, R. J., Mathew, V., Goodman, S. G., Weinshilboum, R. M., Wang, L., Baudhuin, L. M., Lerman, A., Hasan, A., Iturriaga, E., Fu, Y. P., Geller, N., Bailey, K., & Farkouh, M. E. (2019). Clopidogrel pharmacogenetics state-of-the-art review and the TAILOR-PCI study. Circulation: Cardiovascular Interventions, 12(4). https://doi.org/10.1161/CIRCINTERVENTIONS.119.007811