Succinobucol-eluting stents increase neointimal thickening and peri-strut inflammation in a porcine coronary model

Watt, Jonathan and Kennedy, Simon and McCormick, Christopher and Agbani, Ejaife O and McPhaden, Allan and Mullen, Alexander and Czudaj, Peter and Behnisch, Boris and Wadsworth, Roger M and Oldroyd, Keith G (2013) Succinobucol-eluting stents increase neointimal thickening and peri-strut inflammation in a porcine coronary model. Catheterization and Cardiovascular Interventions, 81 (4). 698 - 708.

Abstract

The aim of this study was to assess the efficacy of stent-based delivery of succinobucol alone and in combination with rapamycin in a porcine coronary model. Current drugs and polymers used to coat coronary stents remain suboptimal in terms of long term efficacy and safety. Succinobucol is a novel derivative of probucol with improved antioxidant and anti-inflammatory properties. Polymer-free Yukon stents were coated with 1% succinobucol (SucES), 2% rapamycin (RES) or 1% succinobucol plus 2% rapamycin solutions (SucRES) and compared with a bare metal stent (BMS). RESULTS: The in vivo release profile of SucES indicated drug release up to 28 days (60% drug released at 7 days). 41 stents (BMS, n = 11; SucES, n =10; RES, n = 10; SucRES, n = 10) were implanted in the coronary arteries of 17 pigs. After 28 days, mean neointimal thickness was 0.31 ± 0.14 mm for BMS, 0.51 ± 0.14 mm for SucES, 0.19 ± 0.11 mm for RES and 0.36 ± 0.17 mm for SucRES (p <0.05 for SucES vs. BMS). SucES increased inflammation and fibrin deposition compared with BMS (p <0.05), whereas RES reduced inflammation compared with BMS (p <0.05). In this model, stent-based delivery of 1% succinobucol using a polymer-free stent platform increased neointimal formation and inflammation following coronary stenting.

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