Biotech Values

[jbog]

Targeting Plavix.....

Another biomarker.


Clopidogrel After MI Less Effective in Young Patients With CYP2C19 Variation

NEW YORK -- December 22, 2008 -- Clopidogrel is less effective in patients who have had a myocardial infarction (MI), are aged younger than 45 years and have a certain genetic variation, according to a study published early online and appearing in an upcoming print edition of The Lancet.

In addition, researchers found that these younger patients with the genetic variation were much more likely to die, have another MI, and require urgent repeat coronary intervention or have stent thrombosis.

Gilles Montalescot, MD, Hôpital Pitié-Salpêtrière, Paris, France, and colleagues investigated whether variant 681 G>A (*2) of cytochrome P450 2C19 (CYP2C19) affected long-term prognosis of young patients who were chronically treated with clopidogrel following a MI.

Between 1996 and 2008, 259 patients who survived a first MI and were exposed to clopidogrel treatment for a least a month had their genetic status with respect to the above gene investigated. Of the patients, 73 (28%) were carriers of the gene variation and 186 were non-carriers.

Median clopidogrel exposure was just over a year, and patients were then followed-up every 6 months. Carriers of a particular variation at position 681 on the gene were more than 3.5 times more likely to either die, have another MI, or need urgent repeat coronary intervention.

When looked at alone, thrombosis was 6 times more likely to occur in patients with the variation. The detrimental effect of the variation also persisted from the initiation of clopidogrel treatment until the end of follow-up, up to 8 years later.

Furthermore, after a statistical analysis in which all possible variables were accounted for, the carrying of this genetic variation was the only independent predictor of cardiovascular events, with carriers 4 times more likely to experience an event than non-carriers.

"Our study shows a strong relation between the presence of the CYP2C19*2 allelic variant and recurrent thrombotic coronary events in clopidogrel-treated patients predominantly of European ancestry who survived a heart attack before 45 years of age," the authors wrote.

"Whether the prognostic information associated with the CYP2C19*2 genotype can also be used to guide management of these patients needs to be investigated further. These findings need to be independently replicated...before being extrapolated to older patients or those of non-European ancestry."

In an accompanying comment, Robert F Storey, MD, Cardiovascular Research Unit, University of Sheffield School of Medicine, Sheffield, United Kingdom, said: "Although the fascinating observations of Montalescot and coworkers focus attention on the importance of factors that influence the response to clopidogrel, genotyping of patients with acute coronary syndrome is not necessarily the appropriate solution without further work to validate such an approach."