Gene Variant Linked to Clopidogrel Susceptibility

Presence of variant independently predicts cardiovascular events

TUESDAY, Dec. 23 (HealthDay News) -- In younger patients who have had a heart attack and are taking the anti-platelet drug Plavix (clopidogrel), a variant of a liver enzyme responsible for converting the drug to its active form is an independent predictor of cardiovascular events, according to research published online Dec. 22 in the New England Journal of Medicine and Dec. 23 in The Lancet.

In the Lancet study, Jean-Philippe Collet, M.D., from Hopital Pitie-Salpetriere in Paris, France, and colleagues assessed the presence of the cytochrome P450 2C19 681 G>A variant (CYP2C19*2) associated with reduced susceptibility to clopidogrel in 259 patients who survived a first myocardial infarction. The researchers found that carriers of the variant were significantly more likely to experience death, myocardial infarction or urgent coronary revascularization (15 versus 11 events, hazard ratio 3.69) and stent thrombosis (eight versus four events, HR, 6.02).

In one NEJM study, Tabassome Simon, M.D., Ph.D., of Universite Pierre et Marie Curie in Paris, and colleagues looked at the relation of various allelic variants and the risk of death from any cause, non-fatal stroke or myocardial infarction during a year of follow-up in 2,208 patients who had an acute myocardial infarction and were receiving clopidogrel. They found that those carrying CYP2C19 loss-of-function alleles had a higher rate of subsequent cardiovascular events than those not carrying the alleles. In the other NEJM study, Jessica L. Mega, M.D., of Harvard Medical School in Boston, and colleagues found that among subjects taking clopidogrel, those who were carriers of a reduced-function CYP2C19 allele had less platelet inhibition and more major adverse cardiovascular events, including stent thrombosis, than non-carriers.

"Our results provide strong evidence linking CYP genetic variation to a reduced exposure to the active drug metabolite, less platelet inhibition, and less protection from recurrent ischemic events in persons receiving clopidogrel," Mega and colleagues conclude.

The study by Simon et al. was supported by Pfizer. The study by Mega et al. was supported by Daiichi Sankyo Pharma Development and Eli Lilly Research Laboratories. Authors of all the studies and editorial report financial ties to the pharmaceutical industry.

Abstract - Collet
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Abstract - Simon
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Abstract - Mega
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