Impact of Cytochrome P450 2C19 Reduced-Function Polymorphism on Lesions and Clinical Outcome in Japanese Patients After Drug-eluting Stent Implantation.

We previously reported that the cytochrome P450 (CYP) 2C19 reduced-function polymorphism was associated with decreased responsiveness to clopidogrel and intra-stent thrombus formation, as well as subsequent ischemic events after drug-eluting stent (DES) implantation. However, the relationship between the polymorphism and bleeding events remains unclear. Among 1427 consecutive patients who underwent DES implantation at Kobe University Hospital, 247 patients (341 lesions) were enrolled for this prospective observational study. All patients underwent follow-up optical coherence tomography (OCT) at 8 months and CYP2C19 genotyping. The patients were divided into three groups according to the phenotypic effect of the CYP2C19 polymorphism: extensive metabolizers (EM), intermediate metabolizers (IM), and poor metabolizers (PM). OCT findings, and ischemic and bleeding events were compared among the three groups. The frequency of intra-stent thrombi showed an increasing pattern among the patients with EM, IM, and PM (13.3%, 22.6%, and 33.3%, respectively; p = 0.04). The incidence of major adverse cardiovascular events (MACE) also showed an increase across the three groups from extensive to poor metabolizers (7.8%, 10.5%, and 33.3%, respectively; p < 0.01), whereas the frequency of bleeding showed no significant difference among the groups (15.6%, 19.4%, and 21.2%, respectively; p = 0.69). The CYP2C19 polymorphism is associated with the frequency of MACE, but is not related to the incidence of bleeding after percutaneous coronary intervention in Japanese patients receiving clopidogrel.