Influence of CYP2C19 Phenotype on the Effect of Clopidogrel in Patients Undergoing a Percutaneous Neurointervention Procedure

Clin Pharmacol Ther. 2019 Mar;105(3):661-671. doi: 10.1002/cpt.1067. Epub 2018 Apr 17.

Abstract

This observational retrospective study assessed the antiplatelet response and clinical events after clopidogrel treatment in patients who underwent percutaneous neurointervention, related to CYP2C19 metabolizer status (normal (NM), intermediate/poor (IM-PM), and ultrarapid (UM); inferred from *2, *3, and *17 allele determination). From 123 patients, IM-PM had a higher aggregation value (201.1 vs. 137.6 NM, 149.4 UM, P < 0.05) and lower response rate (37.5% vs. 69.8% NM, 61.1% UM), along with higher treatment change rate (25% vs. 5.7% NM, 10.5% UM). The highest ischemic events incidence occurred in NM (11.3% vs. 6.3% IM, 10.5% UM) and hemorrhagic events in UM (13.2% vs. 0% IM and 3.8% NM). No differences were found regarding ischemic event onset time, while hemorrhagic event frequency in UM was higher with shorter onset time (P = 0.047). CYP2C19 no-function and increased function alleles defined the clopidogrel response. UM patients had increased bleeding risk. Therapeutic recommendations should include dose reduction or treatment change in UM.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angioplasty / adverse effects
  • Angioplasty / trends*
  • Clopidogrel / administration & dosage*
  • Clopidogrel / adverse effects
  • Cytochrome P-450 CYP2C19 / genetics*
  • Cytochrome P-450 CYP2C19 / metabolism
  • Female
  • Hemorrhage / chemically induced
  • Hemorrhage / etiology
  • Hemorrhage / genetics
  • Humans
  • Male
  • Middle Aged
  • Phenotype*
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Retrospective Studies

Substances

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