BACKGROUND: Previous studies have shown that combined therapy with ezetimibe plus simvastatin produced favorable effects on lipid levels and significant reductions in C-reactive protein relative to statin monotherapy. OBJECTIVES: The aim of this study was to examine the anti-proliferative and anti-inflammatory effects of ezetimibe/simvastatin after drug-eluting stent implantation in a porcine coronary overstretch restenosis model. METHODS: Pigs were randomized into two groups in which the coronary arteries (18 pigs, 18 coronaries in each group) had either a sirolimus-eluting stent (SES) or paclitaxel-eluting stent (PES). Stents were deployed with oversizing (stent/artery ratio 1.3:1) in porcine coronary arteries. 10 pigs were taken 10/20 mg of ezetimibe/simvastatin and 8 pigs were not taken ezetimibe/simvastatin. Histopathologic analysis was assessed at 28 days after stenting. RESULTS: In neointima, most inflammatory cells were lymphohistiocytes. Lymphohistiocyte count was significantly lower (217짹169 cells vs. 402짹184 cells, p=0.021), and there were trends toward smaller neointima area and percent area stenosis in SES group compared with PES group, and there was no significant difference in fibrin score between SES and PES group. There were no significant differences in neointima area normalized to injury score and inflammation score between ezetimibe/simvastatin and control group (1.77짹0.68, 1.79짹0.40 vs. 1.79짹0.65, 1.81짹0.71, respectively). Overall, although there was a strong trend toward smaller percent area stenosis in ezetimibe/simvastatin group compared with no statin group, there were no significant differences in neointima area (1.24짹0.80 mm2 vs. 1.38짹0.72 mm2, p=0.5), lymphohistiocyte counts (295짹179 cells vs. 300짹230 cells, p=0.9), and fibrin score (2.06짹0.62 vs. 1.86짹1.03, p=0.6) between ezetimibe/simvastatin group and no statin group, and these no differences in all parameters were found in both SES and PES group. CONCLUSIONS: Combined therapy with ezetimibe plus simvastatin does not inhibit neointimal hyperplasia, inflammatory cell infiltration, and arterial healing after drug-eluting stent implantation in a porcine coronary restenosis model.