Effect of anti-oxidant (carvedilol and probucol) loaded stents in a porcine coronary restenosis model

Abstract

Background: The long-term clinical efficacy of intracoronary stenting is limited by restenosis and delivery by the stent of agents inhibiting cell cycle progression should prevent in-stent neointimal hyperplasia. Carvedilol is an antioxidant that inhibits smooth muscle cell proliferation and migration, whereas probucol is a vascular protectant and reduces stent restenosis by improving the lumen dimension at the stent placement site. Methods and Results: BiodivYsio® phosphorylcholine-coated stents were dip-coated with carvedilol (5 mg/ml) or probucol (50 mg/ml) by immersion in respective methanol solutions. Twenty-four stents (carvedilol=8, probucol=8, control=8) were placed in 12 pigs and histopathologic analysis was done 4 weeks later. Histomorphometry of the carvedilol-coated stent group compared with the control groups showed that the neointimal area decreased by 42% (1.12±0.55 mm2 in the carvedilol group vs 1.92±0.52 mm2 in the control, p=0.004) and the lumen area increased by 20% (5.15±0.90 mm2 vs 4.17±0.87 mm2, p=0.008), resulting in a 43% reduction of the percent area stenosis (18.22±9.6% vs 31.9±9.2%, p=0.002). In the probucol-coated stent group, the lumen area, neointimal area, and %area stenosis did not different significantly from the control group. There were 7.7±2.97% proliferating nuclear cell antigen-positive cells in the carvedilol-coated stent group compared with 17.8±1.45% in the control group (p=0.0001) and 15.9±1.91% in the probucol group (vs control, p=NS). Conclusions: The carvedilol-coated stent, but not the probucol-coated one, inhibited neointimal hyperplasia in a porcine stent restenosis model.