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FDA recommendation for Plavix testing under scrutiny

Kathleen Blanchard's picture
JAMA article questions validity of FDA Plavix warning for genotyping

Not all patients who take the popular ‘blood thinning’ drug Plavix -- clopidrogel --are protected from stroke and heart attack. Studies show people with a variation of CYP2C19, an enzyme manufactured in the liver, don’t metabolize the drug properly. The FDA subsequently put a warning on the drug, recommending genotyping for patients before the medication is prescribed. The warning is now under scrutiny, according to a new study review.

The finding, published in the Journal of the American Medical Association (JAMA), suggests there isn’t enough evidence to recommend routine testing to find out if Plavix works to prevent blood clots.

According to the Food and Drug Administration, “For Plavix to work, enzymes in the liver (particularly CYP2C19) must convert (metabolize) the drug to its active form. Patients who are poor metabolizers of the drug, do not effectively convert Plavix to its active form. In these patients, Plavix has less effect on platelets, and therefore less ability to prevent heart attack, stroke, and cardiovascular death. It is estimated that 2 to 14% of the population are poor metabolizers; the rate varies based on racial background.”

The FDA's warning for Plavix, which is taken by 40 million patients, was added in March, 2010.

In the new review, researchers looked at 32 published studies that included approximately 42,000 patients. The analysis found that even though some patients metabolize Plavix inefficiently, cardiac outcomes were no different than patients without the CYP2C19 variant.

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The cost of genotyping for effectiveness of Plavix is between $200 and $400.

Michael V. Holmes, M.B.B.S., M.Sc., of University College London, and colleagues conducted the systematic review.

"Despite associations between CYP2C19 genotype, clopidogrel metabolism, and platelet aggregation, this systematic review and meta-analysis does not demonstrate a clinically important association of genotype with cardiovascular outcomes with the possible exception of stent thrombosis," the researchers write.

The new finding supports a previous analysis, published in the British Medical Journal (BMJ) that concluded “There is no reliable and robust clinical justification to apply personalised treatment with clopidogrel tailored to CYP2C19 genotype.”

Dr. Steven Nissen who is with the department of cardiovascular medicine at The Cleveland Clinic said the FDA was “…trying to do the right thing but if you look at it in the most rigorous fashion, it wasn't the right answer and it's now time to rethink it." He adds the FDA acted “prematurely” in placing the Plavix warning.

The newest analysis suggests the FDA may have ‘jumped the gun’ by putting a box warning on Plavix last year that suggested patients be genotyped for a variant of the CYP2C19 enzyme. The FDA has not commented. The combined studies mean there is more to be learned about how the drug Plavix (clopidrogel) is metabolized and what, if any impact genotyping has protecting patients from blood clots following stents, angioplasty or stroke.

Image credit: Wikimedia commons
Author: Trounce