A new point-of-care genetic test could rapidly identify CYP2C19*2 carriers who might benefit from nonclopidogrel antiplatelet therapy.

The CYP2C19*2 allele is a common variant associated with high platelet reactivity and increased rates of adverse events after percutaneous coronary intervention (PCI) in patients taking clopidogrel. So far, the inability to perform bedside genetic testing has prevented prospective patient assessment for this allele. Now, a simple point-of-care genetic test (validated by conventional genetic testing) has emerged that identifies CYP2C19*2 carrier status within 60 minutes of activation. Results classify individuals as homozygous for the wild-type allele (*1/*1), heterozygous (*1/*2), or homozygous for the *2 allele (*2/*2).


In a randomized, proof-of-concept study sponsored by the device manufacturer, 200 patients undergoing PCI for acute coronary syndrome or stable angina were assigned to undergo point-of-care genotyping for the CYP2C19*2 allele or to standard treatment. Noncarriers and patients in the standard-treatment group were given 75 mg of clopidogrel daily, and carriers were given 10 mg of prasugrel daily. The primary endpoint was high on-treatment platelet reactivity, defined as a P2Y12 reactivity unit value greater than 234 as measured by the VerifyNow test, at 1 week.

Of 187 patients who completed follow-up, 23 in each group carried at least one CYP2C19*2 allele. At day 7, none of the carriers in the rapid-genotyping group showed high platelet reactivity, compared with seven (30%) in the standard-treatment group (P=0.0092). Sensitivity and specificity of the point-of-care genetic test were 100.0% and 99.3%, respectively.


Citation(s):

Roberts JD et al. Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): A prospective, randomised, proof-of-concept trial. Lancet 2012 May 5; 379:1705.

Beitelshees AL. Personalised antiplatelet treatment: A RAPIDly moving target. Lancet 2012 May 5; 379:1680.