Clinical Utility of CYP2C19 Genotyping to Guide Antiplatelet Therapy in Patients With an Acute Coronary Syndrome or Undergoing Percutaneous Coronary Intervention

Arterioscler Thromb Vasc Biol. 2019 Apr;39(4):647-652. doi: 10.1161/ATVBAHA.118.311963.

Abstract

Current guidelines recommend dual antiplatelet therapy-a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) and aspirin-for patients undergoing percutaneous coronary intervention. Although clopidogrel is the most commonly prescribed P2Y12 inhibitor, it is associated with an increased risk of major adverse cardiovascular events in patients carrying loss-of-function CYP2C19 alleles. In contrast, CYP2C19 genotype does not impact clinical response to prasugrel or ticagrelor. Nevertheless, routine implementation of CYP2C19 genotyping to guide antiplatelet therapy selection has remained controversial because of the lack of large randomized controlled trials evaluating this strategy. Emerging results from registry studies and small clinical trials of CYP2C19 genotype-guided antiplatelet therapy following percutaneous coronary intervention offer new insight and contribute to a growing evidence base that supports the clinical utility of a genotyping strategy to personalize antiplatelet therapy selection.

Keywords: acute coronary syndrome; clopidogrel; coronary intervention; cytochrome P-450 CYP2C19; percutaneous; pharmacogenetics; prasugrel hydrochloride; ticagrelor.

Publication types

  • Review

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / genetics
  • Alleles
  • Biotransformation / genetics
  • Clinical Trials as Topic
  • Clopidogrel / pharmacokinetics
  • Clopidogrel / therapeutic use
  • Cytochrome P-450 CYP2C19 / blood
  • Cytochrome P-450 CYP2C19 / genetics*
  • Cytochrome P-450 CYP2C19 / metabolism
  • Genotype
  • Humans
  • Loss of Function Mutation
  • Meta-Analysis as Topic
  • Patient Selection
  • Percutaneous Coronary Intervention*
  • Platelet Aggregation Inhibitors / pharmacokinetics*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Practice Guidelines as Topic
  • Precision Medicine
  • Purinergic P2Y Receptor Antagonists / pharmacokinetics*
  • Purinergic P2Y Receptor Antagonists / therapeutic use
  • Risk

Substances

  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19