CYP2C19 genotype-guided antiplatelet therapy: promises and pitfalls

Pharmacogenomics. 2020 Aug;21(12):889-897. doi: 10.2217/pgs-2020-0046. Epub 2020 Jul 29.


Pharmacogenetic variants can alter the mechanism of action (pharmacodynamic gene variants) or kinetic processes such as absorption, distribution, metabolism and elimination (pharmacokinetic gene variants). Many initial successes in precision medicine occurred in the context of genes encoding the cytochromes P450 (CYP enzymes). CYP2C19 activates the antiplatelet drug clopidogrel, and polymorphisms in the CYP2C19 gene are known to alter the outcome for patients taking clopidogrel in the context of cardiovascular disease. CYP2C19 loss-of-function alleles are specifically associated with increased risk for coronary stent thrombosis and major adverse cardiovascular events in patients taking clopidogrel following percutaneous coronary intervention. We explore successes and challenges encountered as the clinical and scientific communities advance CYP2C19 genotyping in the context of routine patient care.

Keywords: CYP2C19; Prasugrel; Ticagrelor; clopidogrel; drug-metabolizing enzyme; pharmacogenomics; pharmacokinetics; pleiotropy; polymorphism; precision medicine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute Coronary Syndrome / chemically induced
  • Acute Coronary Syndrome / genetics
  • Animals
  • Cytochrome P-450 CYP2C19 / genetics*
  • Dose-Response Relationship, Drug
  • Drug Substitution / methods
  • Genotype*
  • Humans
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects


  • Platelet Aggregation Inhibitors
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19