Genetic Determinants of P2Y12 Inhibitors and Clinical Implications

Interv Cardiol Clin. 2017 Jan;6(1):141-149. doi: 10.1016/j.iccl.2016.08.010.

Abstract

There is significant interpatient variability in clopidogrel effectiveness, which is due in part to cytochrome P450 (CYP) 2C19 genotype. Approximately 30% of individuals carry CYP2C19 loss-of-function alleles, which have been consistently shown to reduce clopidogrel effectiveness after an acute coronary syndrome and percutaneous coronary intervention. Guidelines recommend consideration of prasugrel or ticagrelor in these patients. A clinical trial examining outcomes with CYP2C19 genotype-guided antiplatelet therapy is ongoing. In the meantime, based on the evidence available to date, several institutions have started clinically implementing CYP2C19 genotyping to assist with antiplatelet selection after percutaneous coronary intervention.

Keywords: CYP2C19; Clopidogrel; Genotype; Pharmacogenomics; Prasugrel; Ticagrelor.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Acute Coronary Syndrome / metabolism
  • Acute Coronary Syndrome / therapy*
  • Alleles
  • Clopidogrel
  • Cytochrome P-450 CYP2C19 / drug effects
  • Cytochrome P-450 CYP2C19 / genetics*
  • Cytochrome P-450 CYP2C19 / metabolism
  • Genotype
  • Humans
  • Percutaneous Coronary Intervention*
  • Polymorphism, Single Nucleotide*
  • Purinergic P2Y Receptor Antagonists / therapeutic use
  • Thrombosis / genetics*
  • Thrombosis / metabolism
  • Thrombosis / prevention & control
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use

Substances

  • Purinergic P2Y Receptor Antagonists
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine