The CYP2C19*2 allele is a common genetic variant that has been associated with a significantly increased risk of major cardiovascular events and stent thrombosis following percutaneous coronary intervention (PCI). In this study a novel point-of-care genetic test was used to identify carriers of the CYP2C19*2 allele and to tailor a pharmacogenetic appriach to dual antiplatelet treatment after PCI.
200 patients were enrolled into this prospective, randomised study. Patients undergoing PCI either electively or following an acute coronary syndrome were randomised to either point-of-care genotyping or to standard treatment. Carriers of the CYP2C19*2 allele were given 10mg of prasugrel daily, whereas all other patients in the trial were give 75mg of clopidogrel daily. The primary endpoint was was the proportion of CYP2C19*2 carriers with high on-treatment platelet reactivity after 1 week of dual antiplatelet treatment.
187 patients completed follow-up, 91 from the rapid genotyping group, and 96 receiving standard treatment; in each group 23 individuals carried at least one CYP2C19*2 allele. None of the 23 carriers in the rapid genotyping group had evidence of inadequate platelet inhibition after seven days, compared with seven (30%) who were given standard treatment (p=0.0092). The point-of-care genetic test had a sensitivity of 100% and a specificity of 99.3%.
This study shows the utility of point-of-care genetic testing at the bedside and shows that treatment of identified CYP2C19*2 carriers with prasugrel can reduce high on-treatment platelet reactivity.
- Roberts JD, Wells GA, Le May MR et al. Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial. Lancet 2012; 379:1705-11.