Recent research has suggested that the CYP2C19*17 allelic variant is associated with increased transcriptional activity, leading to extensive metabolisation of CYP2C19 substrates, which may lead to an enhanced platelet response to clopidogrel treatment. To investigate this further, this study assessed 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 (PCI).

Study investigators enrolled 1524 patients undergoing PCI after pre-treatment with a loading dose of 600 mg clopidogrel. The primary safety end point was the 30-day incidence of bleeding defined according to Thrombolysis in Myocardial Infarction (TIMI) criteria, and the primary efficacy end point was the 30-day incidence of stent thrombosis.

The following results were reported:

• Of the 1524 patients, 902 (59%) were wild-type homozygous for the *17 allelic variant (wt/wt), 546 (36%) were CYP2C19*17 heterozygotes (wt/*17), and 76 (5%) were homozygous (*17/*17) for the mutant CYP2C19*17 allelic variant. Consequently, 622 patients (41%) were carriers of at least one *17 allele. This genotype distribution results in the following allele frequencies: 77.1% for the CYP2C19 wild-type allele versus 22.9% for the CYP2C19*17 mutant allelic variant.
• 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).
• The primary safety end point (combined TIMI major and minor bleedings) within 30 days occurred in 51 patients (3.3%) of the study population. Twelve TIMI major bleedings (0.8%) and 39 TIMI minor bleedings (2.5%) were observed. Forty-five (88%) of the bleeding events observed occurred during the first 24 hours after the procedure. Forty-nine bleedings (96%) were in-hospital bleeding events.
• 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). 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, the primary efficacy endpoint, was found (P=0.79).

The authors concluded that CYP2C19*17 carrier status is significantly associated with enhanced response to clopidogrel and an increased risk of bleeding.