BACKGROUND: The cytochrome P450 (CYP) 2C19 isoenzyme plays an important role in 
clopidogrel metabolization. A recently explored CYP2C19*17 allelic variant has 
been linked to increased transcriptional activity, resulting in extensive 
metabolization of CYP2C19 substrates, which may lead to an enhanced platelet 
response to clopidogrel treatment. The aim of this study was to assess the 
impact of CYP2C19*17 on ADP-induced platelet aggregation, the risk of bleeding, 
and stent thrombosis in clopidogrel-treated patients undergoing percutaneous 
coronary intervention.
METHODS AND RESULTS: The study population included 1524 patients undergoing 
percutaneous coronary intervention after pretreatment with 600 mg clopidogrel. 
Genotypes were determined with a TaqMan assay. ADP-induced platelet aggregation 
was assessed on a Multiplate analyzer. The primary clinical safety end point was 
the 30-day incidence of bleeding defined according to Thrombolysis in Myocardial 
Infarction criteria, and the primary clinical efficacy end point was the 30-day 
incidence of stent thrombosis. For both heterozygous (*wt/*17; n=546) and 
homozygous (*17/*17; n=76) allele carriers, significantly lower ADP-induced 
platelet aggregation values were found compared with wild-type homozygotes 
(*wt/*wt; n=902; P=0.039 and P=0.008, respectively). CYP2C19*17 allele carriage 
was significantly associated with an increased risk of bleeding; the highest 
risk was observed for CYP2C19*17 homozygous patients (P=0.01, chi(2) test for 
trend). Multivariate analysis confirmed the independent association of 
CYP2C19*17 allele carriage with platelet aggregation values (P<0.001) and the 
occurrence of bleeding (P=0.006). No significant influence of CYP2C19*17 on the 
occurrence of stent thrombosis was found (P=0.79).
CONCLUSIONS: CYP2C19*17 carrier status is significantly associated with enhanced 
response to clopidogrel and an increased risk of bleeding.