J Korean Med Sci.  2010 May;25(5):716-722. 10.3346/jkms.2010.25.5.716.

Effects of Combined Therapy with Ezetimibe Plus Simvastatin After Drug-Eluting Stent Implantation in a Porcine Coronary Restenosis Model

• Cho JS
• Jeong MH
• Sim DS
• Hong YJ
• Lim KS
• Kim JH
• Kim HD
• Baek JY
• Yoon HJ
• Her SH
• Jin SW
• Kim JH
• Ahn Y
• Cho JG
• Park JC
• Kang JC

• KMID: 1713955
• DOI: http://doi.org/10.3346/jkms.2010.25.5.716

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 mm2 vs. 1.69+/-0.98 mm2, 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.

Keyword

Stents; Restenosis; Inflammation; Endothelization

MeSH Terms

Animals
Anticholesteremic Agents/administration & dosage
Azetidines/*administration & dosage
Coronary Restenosis/diagnosis/drug therapy/*etiology
*Disease Models, Animal
Drug Combinations
Drug Implants/administration & dosage
Drug-Eluting Stents/*adverse effects
Female
Graft Occlusion, Vascular/diagnosis/*drug therapy/*etiology
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage
Simvastatin/*administration & dosage
Swine
Treatment Outcome
Anticholesteremic Agents
Azetidines
Drug Combinations
Drug Implants
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Simvastatin

Figure

• 

  Fig. 1 Neointima area was significantly smaller (A) and percent area stenosis was significantly lower (B) in ezetimibe/simvastatin group compared with control group.

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  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.

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  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.

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  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.

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