title: Impact of CYP2C19 genetic testing on provider prescribing patterns for antiplatelet therapy after acute coronary syndromes and percutaneous coronary intervention.
abstract: BACKGROUND
  Patients treated with clopidogrel who have ≥1 loss of function alleles for CYP2C19 have an increased risk for adverse cardiovascular events. In 2010, the US Food and Drug Administration issued a boxed warning cautioning against the use of clopidogrel in such patients. We sought to assess the impact of CYP2C19 genetic testing on prescribing patterns for antiplatelet therapy among patients with acute coronary syndrome or percutaneous coronary intervention.
  
  
  RESULTS
  Patients with recent acute coronary syndrome or percutaneous coronary intervention prescribed clopidogrel were offered CYP2C19 testing. Genotype and phenotype results were provided to patients and their physicians, but no specific treatment recommendations were suggested. Patients were categorized based on their genotype (carriers versus noncarriers) and phenotype (extensive, intermediate, and poor metabolizers). The primary outcome was intensification in antiplatelet therapy defined as either dose escalation of clopidogrel or replacement of clopidogrel with prasugrel. Between July 2010 and April 2012, 6032 patients were identified, and 499 (8.3%) underwent CYP2C19 genotyping, of whom 146 (30%) were found to have ≥1 reduced function allele, including 15 (3%) with 2 reduced function alleles. Although reduced function allele carriers were significantly more likely than noncarriers to have an intensification of their antiplatelet therapy, only 20% of poor metabolizers of clopidogrel had their antiplatelet therapy intensified.
  
  
  CONCLUSIONS
  Providers were significantly more likely to intensify antiplatelet therapy in CYP2C19 allele carriers, but only 20% of poor metabolizers of clopidogrel had an escalation in the dose of clopidogrel or were switched to prasugrel. These prescribing patterns likely reflect the unclear impact and evolving evidence for clopidogrel pharmacogenomics.
authors.affiliation: Section of Cardiovascular Medicine, Department of Medicine, Yale School of Medicine, and Center for Outcomes Research and Evaluation, Yale New Haven Health System, New Haven, CT.
authors.forename: Nihar R
authors.initials: NR
authors.lastname: Desai
authors.forename: William J
authors.initials: WJ
authors.lastname: Canestaro
authors.forename: Pavlo
authors.initials: P
authors.lastname: Kyrychenko
authors.forename: Donald
authors.initials: D
authors.lastname: Chaplin
authors.forename: Lori A
authors.initials: LA
authors.lastname: Martell
authors.forename: Troyen
authors.initials: T
authors.lastname: Brennan
authors.forename: Olga S
authors.initials: OS
authors.lastname: Matlin
authors.forename: Niteesh K
authors.initials: NK
authors.lastname: Choudhry
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D000368:Aged; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001711:Biotransformation / Q000235:genetics; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D057915:Drug Substitution; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006282:Health Personnel / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010597:Pharmacogenetics; D010879:Piperazines / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000235:genetics / Q000517:prevention & control*; D010818:Practice Patterns, Physicians'; D000068799:Prasugrel Hydrochloride; D017384:Sequence Deletion / Q000235:genetics; D013876:Thiophenes / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine
keywords: antiplatelet agents; pharmacogenetics; quality of health care