Clopidogrel may not be the best antiplatelet drug for carriers of CYP2C19*2

Some people respond poorly to antiplatelet prophylaxis with clopidogrel and have recurrent cardiovascular events. Genomic analyses have investigated several candidate genes that might explain this phenomenon, but the first genome wide association study provides a fuller picture.

The researchers first studied 429 healthy Amish people to minimise the risk of confounding by lifestyle and use of medications. All participants took clopidogrel for seven days, after which an association was found between the loss of function cytochrome P450 (CYP) 2C19*2 variant and a reduced effect of clopidogrel on blood thinning. This fits with previous research, which showed that the drug’s antiplatelet effect depends on its being converted to an active metabolite, a process in which hepatic cytochrome P450 isoenzymes play a crucial part.

The findings were replicated in 227 adults at high cardiovascular risk who were given clopidogrel just before undergoing non-emergent percutaneous coronary intervention. Moreover, the findings in this population showed that carriers of the CYP2C19*2 variant were more likely than non-carriers (20.9% v 10.0%) to have a cardiovascular ischaemic event or to die in the year after the procedure (hazard ratio 2.42, 95% CI 1.18 to 4.99), but only if they were taking clopidogrel⇑.

The linked editorial (p 896) says pharmacogenomic testing will soon be able to identify people in whom approaches other than taking clopidogrel would decrease ischaemic events. We need trials to find out whether this would apply to all carriers of CYP2C19*2 or only some.