Document Detail


Inhibition of experimental neointimal hyperplasia and neoatherosclerosis by local, stent-mediated delivery of everolimus.
MedLine Citation:
PMID:  22841285     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
INTRODUCTION: A novel self-expanding, drug-eluting stent was designed to slowly release everolimus in order to prevent restenosis after percutaneous peripheral intervention. The purpose of this experimental animal study was to test the hypothesis that long-term local, stent-mediated delivery of everolimus would reduce neointimal hyperplasia in porcine iliac arteries. METHODS: The iliac arteries of 24 Yucatan mini-swine were percutaneously treated with overlapping 8- × 28-mm self-expanding nitinol stents loaded with everolimus (225 μg/cm(2) stent surface area) formulated in a poly(ethylene-co-vinyl alcohol) copolymer intended to deliver the drug in a sustained fashion over about 6 months (drug-eluting stent [DES]). Bare nitinol self-expanding stents (bare metal stent [BMS]) were implanted in an identical fashion on the contralateral side to serve as controls. After 3, 6, or 12 months, the animals were sacrificed and the stented arteries perfusion-fixed for histomorphometric analysis. RESULTS: The chronic presence of everolimus in arterial tissue reduced stent-induced inflammation after 3 months (inflammation score BMS 2.29 ± 0.44 vs DES 0.17 ± 0.17; P = .001) and 6 months (BMS 2.06 ± 0.43 vs DES 0.50 ± 0.5; P = .007), although some late inflammation was observed after drug exhaustion (BMS 1.00 ± 0.25 vs DES 2.56 ± 0.62 after 12 months; P = not significant [NS]). Treatment with locally delivered everolimus significantly reduced neointimal hyperplasia after 3 months (neointimal thickness BMS 0.79 ± 0.20 vs DES 0.37 ± 0.04 mm; P = .03) and 6 months (BMS 0.73 ± 0.14 vs DES 0.41 ± 0.08 mm; P = .05), although the effect had dissipated after 12 months (BMS 0.68 ± 0.11 vs DES 0.67 ± 0.11 mm; P = NS). Remarkably, stent-induced neoatherosclerosis, characterized by the histologic presence of foamy macrophages and cholesterol clefts, was significantly attenuated by treatment with everolimus (atherogenic change scores at 3 months BMS 0.56 ± 0.15 vs DES 0.04 ± 0.04; P = .003; 6 months BMS 0.84 ± 0.23 vs DES 0.00 ± 0.00; P = .004; and 12 months BMS 0.09 ± 0.10 vs DES 0.19 ± 0.19; P = NS). CONCLUSIONS: In this experimental animal model, local arterial stent-mediated delivery of everolimus inhibited the formation of neointimal hyperplasia and neoatherosclerosis during the first 6 months. The effect was transient, however, as arterial morphology and histology appeared similar to control stented arteries after 12 months.
Authors:
Hugh Q Zhao; Alexander Nikanorov; Renu Virmani; Lewis B Schwartz
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-26
Journal Detail:
Title:  Journal of vascular surgery : official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter     Volume:  -     ISSN:  1097-6809     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8407742     Medline TA:  J Vasc Surg     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.
Affiliation:
Abbott Laboratories, Abbott Park, Ill.
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