title: Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial.
abstract: BACKGROUND
  Prospective assessment of pharmacogenetic strategies has been limited by an inability to undertake bedside genetic testing. The CYP2C19*2 allele is a common genetic variant associated with increased rates of major adverse events in individuals given clopidogrel after percutaneous coronary intervention (PCI). We used a novel point-of-care genetic test to identify carriers of the CYP2C19*2 allele and aimed to assess a pharmacogenetic approach to dual antiplatelet treatment after PCI.
  
  
  METHODS
  Between Aug 26, 2010, and July 7, 2011, 200 patients were enrolled into our prospective, randomised, proof-of-concept study. Patients undergoing PCI for acute coronary syndrome or stable angina were randomly assigned to rapid point-of-care genotyping or to standard treatment. Individuals in the rapid genotyping group were screened for the CYP2C19*2 allele. Carriers were given 10 mg prasugrel daily, and non-carriers and patients in the standard treatment group were given 75 mg clopidogrel daily. The primary endpoint was the proportion of CYP2C19*2 carriers with high on-treatment platelet reactivity (P2Y12 reactivity unit [PRU] value of more than 234) after 1 week of dual antiplatelet treatment, which is a marker associated with increased adverse cardiovascular events. Interventional cardiologists and data analysts were masked to genetic status and treatment. Patients were not masked to treatment allocation. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, NCT01184300.
  
  
  RESULTS
  After randomisation, 187 patients completed follow-up (91 rapid genotyping group, 96 standard treatment). 23 individuals in each group carried at least one CYP2C19*2 allele. None of the 23 carriers in the rapid genotyping group had a PRU value of more than 234 at day 7, compared with seven (30%) given standard treatment (p=0·0092). The point-of-care genetic test had a sensitivity of 100% (95% CI 92·3-100) and a specificity of 99·3% (96·3-100).
  
  
  CONCLUSIONS
  Point-of-care genetic testing after PCI can be done effectively at the bedside and treatment of identified CYP2C19*2 carriers with prasugrel can reduce high on-treatment platelet reactivity.
  
  
  BACKGROUND
  Spartan Biosciences.
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Roberts
authors.forename: George A
authors.initials: GA
authors.lastname: Wells
authors.forename: Michel R
authors.initials: MR
authors.lastname: Le May
authors.forename: Marino
authors.initials: M
authors.lastname: Labinaz
authors.forename: Chris
authors.initials: C
authors.lastname: Glover
authors.forename: Michael
authors.initials: M
authors.lastname: Froeschl
authors.forename: Alexander
authors.initials: A
authors.lastname: Dick
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Marquis
authors.forename: Edward
authors.initials: E
authors.lastname: O'Brien
authors.forename: Sandro
authors.initials: S
authors.lastname: Goncalves
authors.forename: Irena
authors.initials: I
authors.lastname: Druce
authors.forename: Alexandre
authors.initials: A
authors.lastname: Stewart
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gollob
authors.forename: Derek Y F
authors.initials: DY
authors.lastname: So
mesh_terms: D054058:Acute Coronary Syndrome / Q000628:therapy; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010879:Piperazines / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019095:Point-of-Care Systems; D000068799:Prasugrel Hydrochloride; D057285:Precision Medicine; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine