Effects of combined therapy with ezetimibe plus simvastatin after drug-eluting stent implantation in a porcine coronary restenosis model

Abstract

The aim of this study was to examine the anti-proliferative and anti-inflammatory effects of ezetimibe/simvastatin (E/S) after drug-eluting stent (DES) implantation in a porcine coronary restenosis model. Pigs were randomized into two groups in which the coronary arteries (23 pigs) had DES. Stents were deployed with oversizing (stent/artery ratio 1.3:1) in porcine coronary arteries. Fifteen pigs were taken 10/20 mg of E/S and eight pigs were not taken E/S. Histopathologic analysis was assessed at 28 days after stenting. In neointima, most inflammatory cells were lymphohistiocytes. Lymphohistiocyte count was not different between two groups (337+/-227 vs. 443+/-366 cells, P=0.292), but neointima area was significantly smaller (1.00+/-0.49 mm(2) vs. 1.69+/-0.98 mm(2), P=0.021) and percent area stenosis was significantly lower (23.3+/-10% vs. 39+/-19%, P=0.007) in E/S group compared with control group. There were no significant differences in fibrin score (1.99+/-0.79 vs. 1.81+/-0.88, P=0.49), endothelial score (1.75+/-0.66 vs. 1.80+/-0.59, P=0.79), and the percent of endothelium covered lumen (43+/-21% vs. 45+/-21%, P=0.84) between E/S group and control group. Combined therapy with ezetimibe and simvastatin inhibits neointimal hyperplasia, but does not inhibit inflammatory infiltration and arterial healing after DES implantation in a porcine coronary restenosis model.

Keywords: Endothelization; Inflammation; Restenosis; Stents.

Fig. 1

Neointima area was significantly smaller (A) and percent area stenosis was significantly lower (B) in ezetimibe/simvastatin group compared with control group.

Fig. 2

Drug-eluting stented porcine coronary arteries (Methyl methacrylate staining: ×25, A, B and ×100, C, D). Neointima area was larger and percent area stenosis was higher in control group compared with ezetimibe/simvastatin group.

Fig. 3

Carstair's fibrin stain (×200) for determining delayed arterial healing according to discriminate fibrin score that is not different between ezetimibe/simvastatin (A) and (B) control groups.

Fig. 4

There was no significant differences in fibrin score (A), endothelial score (B), and the percent of enthelium covered lumen (C) between ezetimibe/simvastatin group and control group.