Clopidogrel Pharmacogenetics

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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)
Pages (from-to)e007811
JournalCirculation. Cardiovascular interventions
Volume12
Issue number4
DOIs
StatePublished - Apr 1 2019

Fingerprint

clopidogrel
Pharmacogenetics
Percutaneous Coronary Intervention
Alleles
Drug Labeling
Point-of-Care Systems
Pragmatic Clinical Trials
United States Food and Drug Administration
Complementary Therapies
Carrier Proteins
Therapeutics
Blood Platelets
Genotype
Guidelines
Cytochrome P-450 CYP2C19

Keywords

  • clinical trial
  • clopidogrel
  • cytochrome P450 CYP2C19
  • drug labeling
  • genetics
  • humans
  • pharmacogenetics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Pereira, N. L., Rihal, C., So, D. Y. F., Rosenberg, Y., Lennon, R. J., Mathew, V., ... Farkouh, M. E. (2019). Clopidogrel Pharmacogenetics. Circulation. Cardiovascular interventions, 12(4), e007811. https://doi.org/10.1161/CIRCINTERVENTIONS.119.007811

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

In: Circulation. Cardiovascular interventions, Vol. 12, No. 4, 01.04.2019, p. e007811.

Research output: Contribution to journalArticle

Pereira, NL, Rihal, C, So, DYF, Rosenberg, Y, Lennon, RJ, Mathew, V, Goodman, SG, Weinshilboum, RM, Wang, LM, Baudhuin, LM, Lerman, A, Hasan, A, Iturriaga, E, Fu, YP, Geller, N, Bailey, KR & Farkouh, ME 2019, 'Clopidogrel Pharmacogenetics', Circulation. Cardiovascular interventions, vol. 12, no. 4, pp. e007811. https://doi.org/10.1161/CIRCINTERVENTIONS.119.007811
Pereira NL, Rihal C, So DYF, Rosenberg Y, Lennon RJ, Mathew V et al. Clopidogrel Pharmacogenetics. Circulation. Cardiovascular interventions. 2019 Apr 1;12(4):e007811. https://doi.org/10.1161/CIRCINTERVENTIONS.119.007811
Pereira, Naveen Luke ; Rihal, Charanjit ; So, Derek Y.F. ; Rosenberg, Yves ; Lennon, Ryan J. ; Mathew, Verghese ; Goodman, Shaun G. ; Weinshilboum, Richard M ; Wang, Liewei M ; Baudhuin, Linnea M. ; Lerman, Amir ; Hasan, Ahmed ; Iturriaga, Erin ; Fu, Yi Ping ; Geller, Nancy ; Bailey, Kent R ; Farkouh, Michael E. / Clopidogrel Pharmacogenetics. In: Circulation. Cardiovascular interventions. 2019 ; Vol. 12, No. 4. pp. e007811.
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