Association of cytochrome P450 2C19*2 polymorphism with clopidogrel response variability and cardiovascular events in Koreans treated with drug-eluting stents.

BACKGROUND

Although East Asians carry the cytochrome P450 (CYP) 2C192 allele more frequently than do Caucasians, the impact of the CYP2C192 allele on clopidogrel pharmacodynamics and clinical outcomes is unknown.

OBJECTIVE

To evaluate the effect of CYP2C19 variants on clopidogrel pharmacodynamics and long-term prognosis in East Asian patients with drug-eluting stents (DES).

METHODS

DES-treated patients taking dual antiplatelet therapy were enrolled from a Korean multicentre genetic registry. The CYP2C19*2 allele was genotyped using the Taqman method (n=2146), and on-treatment platelet reactivity was measured with the VerifyNow P2Y12 assay (n=1415).

RESULTS

1011 patients (47%) carried at least one CYP2C192 allele. The mean on-treatment platelet reactivity was significantly higher in carriers than in non-carriers (250±76 vs 231±83 P2Y12 reaction unit, p<0.001). For up to 12 months' follow-up, the composite of cardiovascular death, non-fatal myocardial infarction and stent thrombosis was significantly higher in carriers of the CYP2C192 allele than non-carriers (2.0% vs 0.8%, p=0.02). On landmark analysis, there was no difference in clinical outcome after 12 months between the groups.

CONCLUSION

The CYP2C19*2 genetic variant may be associated with worse outcome in Korean patients treated exclusively with DES and dual-antiplatelet therapy due to a significant increase in cardiac death, myocardial infarction or stent thrombosis.