Clopidogrel: indication-specific pharmacogenetics

An article published in the May edition of Clinical Pharmacology & Therapeutics reviews the mixed results seen in different studies for the association between adverse cardiovascular events and the CYP2C19*2 allele in patients taking clopidogrel.

The CYP2C19*2 allele confers loss of function of the CYP2C19 enzyme and thus poor metabolism of clopidogrel (view the role of CYP2C19 in the PharmGKB Clopidogrel Pharmacokinetics Pathway). Poor metabolism of clopidogrel results in less active metabolite and thus reduced inhibition of platelet aggregation - this is associated with an increased risk of blood clot formation, which can lead to adverse cardiovascular events.

The review concludes that the evidence supports an association between high risk for adverse cardiovascular events in patients with the CYP2C19*2 allele who are prescribed clopidogrel following percutaneous coronary intervention (PCI), and genotyping in these cases should be used to guide therapy, but not for other indications.

Read the article:

Clopidogrel: a case for indication-specific pharmacogenetics. 
Johnson JA, Roden DM, Lesko LJ, Ashley E, Klein TE, Shuldiner AR.
Clin Pharmacol Ther. 2012 May;91(5):774-6.