BACKGROUND: Whether cytochrome P450 (CYP) 3A4 metabolized statins attenuate the antiplatelet effect and clinical benefits of clopidogrel, which is metabolized by cytochrome P450 (CYP) 3A4, is on debating. OBJECTIVES: We evaluated how CYP3A4 metabolized statin (atorvastatin) and non-CYP3A4 metabolized super-statin (rosuvastatin) influence the antiplatelet effect and clinical benefits when given concomitantly with clopidogrel in the era of drug-eluting stent (DES). METHODS: We assigned 200 consecutive patients with 235 native lesions who underwent successful DES implantation. Patients were randomized to take either atorvastatin 10mg QD (group I: 100 patients, 121 lesions) or rosuvastatin 10mg QD (group II: 100 patients, 114 lesions) with clopidogrel 300mg loading at least 12 hours before procedure. All patients were on clopidogrel 75mg QD and statin together during 9 months. The antiplatelet effect of clopidogrel was assessed at 48hours after DES implantation, using the ultegra rapid platelet function assay (RPFA)-P2Y12 (VerifyNow짰 assay). RESULTS: There were no differences in terms of clinical characteristics between the two groups except a higher prevalence of unstable angina in group I (56 vs. 44%, p = 0.037). Two groups showed a similar pattern in angiographic and procedural parameters. The prevalence of clopidogrel resistance, defined as % platelet inhibition ���20%, did not differ (group I, 42% vs. group II, 40%: p = 0.768). In addition, a degree of platelet inhibition in group I was nearly same with that of group II (% platelet inhibition: group I, 31 짹 24% vs. group II, 31 짹 24%, p = 0.925). A primary end point (death, myocardial infarction, target vessel revascularization, stent thrombosis within 9 months) was not different between the two groups (4 vs. 4%, p = 1.000) without an occurrence of stent thrombosis. There were no differences in major bleeding (3 vs. 0%, p = 0.206) and restenosis, defined as ���50% (7 vs. 9%, p = 1.000) during 9 months. CONCLUSIONS: The antiplatelet effect and clinical benefits of clopidogrel in patients undergoing DES implantation is not attenuated by long-term taken CYP3A4-metabolized statin.