Physician response to implementation of genotype-tailored antiplatelet therapy

Clin Pharmacol Ther. 2016 Jul;100(1):67-74. doi: 10.1002/cpt.331. Epub 2016 Feb 17.

Abstract

Physician responses to genomic information are vital to the success of precision medicine initiatives. We prospectively studied a pharmacogenomics implementation program for the propensity of clinicians to select antiplatelet therapy based on CYP2C19 loss-of-function variants in stented patients. Among 2,676 patients, 514 (19.2%) were found to have a CYP2C19 variant affecting clopidogrel metabolism. For the majority (93.6%) of the cohort, cardiologists received active and direct notification of CYP2C19 status. Over 12 months, 57.6% of poor metabolizers and 33.2% of intermediate metabolizers received alternatives to clopidogrel. CYP2C19 variant status was the most influential factor impacting the prescribing decision (hazard ratio [HR] in poor metabolizers 8.1, 95% confidence interval [CI] [5.4, 12.2] and HR 5.0, 95% CI [4.0, 6.3] in intermediate metabolizers), followed by patient age and type of stent implanted. We conclude that cardiologists tailored antiplatelet therapy for a minority of patients with a CYP2C19 variant and considered both genomic and nongenomic risks in their clinical decision-making.

MeSH terms

  • Age Factors
  • Aged
  • Clinical Decision-Making
  • Clopidogrel
  • Cytochrome P-450 CYP2C19 / genetics*
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Pharmacogenetics*
  • Platelet Aggregation Inhibitors / metabolism
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Practice Patterns, Physicians' / statistics & numerical data*
  • Precision Medicine / methods
  • Prospective Studies
  • Stents
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / metabolism
  • Ticlopidine / therapeutic use

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • Ticlopidine