Inhibition of experimental neointimal hyperplasia and neoatherosclerosis by local, stent-mediated delivery of everolimus

Autor: Hugh Q. Zhao, Renu Virmani, Alexander Nikanorov, Lewis B. Schwartz
Jazyk: angličtina
Předmět:
Zdroj: Journal of Vascular Surgery. (6):1680-1688
ISSN: 0741-5214
DOI: 10.1016/j.jvs.2012.04.022
Popis: IntroductionA novel self-expanding, drug-eluting stent (DES) 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.MethodsThe iliac arteries of 24 Yucatan mini-swine were percutaneously treated with overlapping 8- × 28-mm self-expanding nitinol stents loaded with everolimus (225 μg/cm2 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 (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.ResultsThe 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).ConclusionsIn 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.Clinical RelevanceAtherosclerotic vascular disease and its sequelae remain the single greatest killers in the world. Significant advances have been made in the development of endovascular techniques for both coronary and peripheral interventions. Although almost always successful technically, 30% to 50% of stent-based coronary and peripheral interventions will fail during the first year. In the coronary arteries, this problem has largely been circumvented by the development of drug-eluting stents. To date, however, drug-eluting stents have been found to be only marginally helpful in the peripheral circulation. 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 peripheral arteries.
Databáze: OpenAIRE
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