December 27th, 2011
Clopidogrel Testing Comes Under Fire
The phenomenon of clopidogrel resistance has been much discussed, but no consensus has emerged about the best, or any, response to the problem. Now a review published in JAMA finds no clinically relevant relationship between the CYP2C19 genotype and cardiovascular events.
Michael Holmes and colleagues performed a meta-analysis of 32 studies involving CYP 2C19 genotyping and more than 42,000 patients. In the observational studies of patients receiving clopidogrel, the investigators found an association between CYP 2C19 alleles and outcomes. However, they also found evidence of small-study bias, and when only larger studies were included the association was much diminished. In randomized trials, the clopidogrel genotype had no effect on outcome.
In an accompanying editorial, Steven Nissen writes that attempts to integrate clopidogrel testing in clinical practice, including a boxed warning about clopidogrel resistance from the FDA, have been premature:
No matter how promising, pharmacogenetic approaches to treatment must withstand the same scrutiny required of all therapeutic advances — careful evaluation through well-designed randomized clinical trials.
In the absence of a large randomized controlled trial demonstrating the benefits of the clopidogrel pharmacogenomics, writes Nissen, “physicians should use CYP2C19 or platelet reactivity testing rarely, if ever, and interpret the results with caution.”
[EDITOR’S NOTE: We’ve closed comments on this post to focus the discussion over at this related piece by David Hillis and Rick Lange. Please join the discussion there!]