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

Zhao HQ, Nikanorov A, Virmani R, et al (Abbott Laboratories, Abbott Park, IL; CVPath Inst, Inc, Gaithersburg, MD) J Vasc Surg 56:1680-1688, 2012^§

Abstract

Introduction

A 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.

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/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.

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).

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

1. Muscle Adaptation in Response to Supervised Exercise Training for Intermittent Claudication
2. Follow-Up of Endovascular Treatment for Trans-Atlantic Inter-Society Consensus II Type B Iliac Lesions in Patients Aged <50 Years
3. of Gender and Age on Outcomes of Tibial Artery Endovascular Interventions in Critical Limb Ischemia
4. of Descending Aortic Pathology and Evaluation of the Impact of Thoracic Endovascular Aortic Repair: A Population-based Study in England and Wales from 1999 to 2010

Stay updated, free articles. Join our Telegram channel

Join