Korean Circ J.  2015 Mar;45(2):110-116. 10.4070/kcj.2015.45.2.110.

Effect of Pretreatment of Ezetimibe/Simvastatin on Arterial Healing and Endothelialization after Drug-Eluting Stent Implantation in a Porcine Coronary Restenosis Model

• Sim DS
• Jeong MH
• Park DS
• Kim JH
• Lim KS
• Kim HK
• Kim SS
• Cho JY
• Jeong HC
• Park KH
• Hong YJ
• Kim JH
• Ahn Y
• Cho JG
• Park JC

• KMID: 2297877
• DOI: http://doi.org/10.4070/kcj.2015.45.2.110

Abstract

BACKGROUND AND OBJECTIVES
We sought to evaluate the effect of the early use of ezetimibe/simvastatin (Vytorin(R)) on arterial healing and endothelialization after the implantation of a drug-eluting stent (DES) in a porcine model of coronary restenosis.
MATERIALS AND METHODS
A total of 20 pigs (40 coronary arteries) were randomly allocated to a pretreatment or no treatment group. The pretreatment group (n=20) received oral ezetimibe/simvastatin (10/20 mg) daily for 7 days before stenting and the no pretreatment group (n=20) did not. All pigs were treated with ezetimibe/simvastatin (10/20 mg) daily after stenting for 4 weeks. Stenting was performed using a bare-metal stent (BMS, n=10) and three types of DES: biolimus A9-eluting stent (BES, n=10), zotarolimus-eluting stent (ZES, n=10), and everolimus-eluting stents (EES, n=10). Four weeks later, pigs underwent a follow-up coronary angiography and were sacrificed for histopathologic analysis.
RESULTS
There were no significant differences between the pretreatment and no pretreatment groups in the internal elastic lamina area, lumen area, neointima area, stenotic area, injury score, fibrin score, and inflammation score. In both groups, the fibrin score was higher in pigs with DES than in BMS, particularly in ZES and EES. The inflammatory score was not different between DES and BMS.
CONCLUSION
In a porcine model of coronary restenosis, pretreatment with ezetimibe/simvastatin before DES implantation failed to improve arterial healing and endothelialization compared to treatment after stenting.

Keyword

Coronary restenosis; Drug-eluting stents; Ezetimibe; Hydroxymethylglutaryl-CoA reductase inhibitors

MeSH Terms

Coronary Angiography
Coronary Restenosis*
Drug-Eluting Stents*
Fibrin
Follow-Up Studies
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Inflammation
Neointima
Stents
Swine
Ezetimibe
Fibrin
Hydroxymethylglutaryl-CoA Reductase Inhibitors

Figure

• 

  Fig. 1 The hematoxylin-eosin stain (A-D) and Carstair's fibrin stain (E-H) (magnitude×20) by stent type in swine pretreated with ezetimibe/simvastatin. A and E: BES, B and F: ZES, C and G: EES, D and H: BMS. Greater fibrin deposition and inflammation around the stent struts are shown in DES, particularly in ZES and EES. BES: biolimus A9-eluting stent, BMS: bare-metal stent, DES: drug-eluting stent, EES: everolimus-eluting stent, ZES: zotarolimus-eluting stent.

• 

  Fig. 2 The hematoxylin-eosin stain (A-D) and Carstair's fibrin stain (E-H) (magnitude×20) by stent type in swine without ezetimibe/simvastatin pretreatment. A and E: BES, B and F: ZES, C and G: EES, D and H: BMS. Greater fibrin deposition and inflammation around the stent struts are observed in DES, compared to BMS. EES shows the most severe inflammatory cell infiltration. BES: biolimus A9-eluting stent, BMS: bare-metal stent, DES: drug-eluting stent, EES: everolimus-eluting stent, ZES: zotarolimus-eluting stent.

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