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.
FINDINGS: 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).
INTERPRETATION: 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.
FUNDING: Spartan Biosciences.