Pharmacogenetics Newsletter

Volume 1, Issue 7, 07/15/2009

Question

What influences do genetic polymorphisms to cytochrome P-450 (CYP) 2C19 have on cardiovascular disease (CVD) outcomes in patients taking clopidogrel (Plavix®)?

Answer

The use of clopidogrel (PlavixÒ) along with aspirin are increasing due to their benefits in both primary and secondary prevention of cardiovascular disease (CVD) and now more importantly in patients with drug eluting stents.(1-3)  However, a number of studies have shown that several factors can contribute to clopidogrel's antiplatelet efficacy which can translate into clinically relevant endpoints.(4-8)  Such factors include smoking status and drug interactions with medications (i.e., proton pump inhibitors, certain calcium channel blockers) known to decrease the activation of clopidogrel through the cytochrome P-450 (CYP) enzyme system.(9-11)  In addition to these factors, it is now known that genetic polymorphisms (or variations) to CYP2C19 can also contribute to clopidogrel activation and its ability to adequately inhibit ADP-induced platelet aggregation (see the table below).(12-18) 

As it relates to CYP2C19, there are several known single-nucleotide polymorphisms (SNP) that can significantly influence the activity of that enzyme.(19-25)  The majority of the population around the world have the.....

There is a table with this newsletter that summarizes all of the studies related to this topic.

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