March 28th, 2012
Proof-of-Concept for Bedside Rapid Genotyping Test of CYP2C19
Larry Husten, PHD
A new point-of-care test can rapidly identify people with a common genetic variant associated with impaired clopidogrel function. The authors claim that this is the first study to demonstrate the feasibility of delivering a genetic test at bedside.
In an article published online in the Lancet, Jason Roberts and colleagues report on a new point-of-care test that can identify people who have a common variant of the CYP2c19 gene associated with reduced clopidogrel effectiveness. In their “proof-of-concept” study, 200 patients undergoing PCI were randomized to standard therapy with clopidogrel or to the new test. Patients found to have the CYP2C19*2 allele received prasugrel instead of clopidogrel.
Each group had 23 patients who carried at least one CYP2C19*2 allele. Among these patients, no patients in the test group, and 7 patients (30%) in the control group, were found to have high on-treatment platelet reactivity (PRU) after 1 week of treatment. At 7 and 30 days, there were no ischemic events in either group and no significant differences in major or minor bleeding.
The investigators write that their study “confirms the potential clinical benefits associated with a personalised approach to antiplatelet treatment with selective use of P2Y12 inhibitors in patients at increased risk of adverse events with clopidogrel,” but they also noted that the “major limitation” of their study “was use of a surrogate endpoint to assess clinical efficacy.”
In an accompanying comment, Amber L. Beitelshees notes that “many clinicians do not know what action to take, if any” until the completion of large trials that are in progress. Earlier studies testing the platelet hypothesis may have failed, she says, because new evidence suggests that benefits of genotyping or platelet function tests may be confined to the PCI population. The new rapid genotyping test will make it easier “for incorporation into clinical care in the catheterisation laboratory.”
Testing for high on treatment platelet reactivity has been available for quite some time via the VerifyNow assay, without widespread use despite actionable treatment based on its results (switching to another anti-platelet agent). Its not completely clear that genetic testing provides unique and independent information (especially when the outcome is HTPR!). Are there specific clinical scenarios where genetic testing may be preferred?