The effect of the carvedilol-loaded BiodivYsioTM DD stent on the inhibition of neointimal proliferation in a porcine coronary stent restenosis model

Kim, Weon; Jeong, Myung Ho; Cha, Kwang Soo; Lee, Seung Hyun; Hong, Young Joon; Kim, Ju Han; Ahn, Young Keun; Park, Ok Young; Kim, Mu Hyun; Cho, Jeong Gwan; Park, Jong Chun; Kang, Jung Chaee

Abstract

BACKGROUND: Carvedilol is a beta- and alpha-receptor blocker, a direct inhibitor of smooth muscle cell proliferation and migration, and produces a significant suppression of neointimal hyperplasia in rat carotid injury model. We tested whether carvedilol stent coating is effective in preventing neointimal formation in a porcine model of stent restenosis.
METHODS
BiodivYsio phosphorylcholine-coated stents were dip-coated with carvedilol at the concentrations of 0, 7, 96 and 154 micrometer/stent by the immersion in a methanolic carvedilol followed by the evaporation of the solvent. Thirty-two stents, 8 stents per each concentration, were deployed in the porcine coronary arteries. The treatment effect was assessed at 28 days after stent implantation.
RESULTS
Angiographic minimal lumen diameter and late loss index were similar among the four groups. On histomorphometry, neointimal area decreased by 58% and lumen area increased by 20%, resulting in a 58% reduction of percent in-stent stenosis in 7 micrometer carvedilol/stent (p=0.002, 0.008 and 0.004, respectively, 7 micrometer vs. 0 micrometer carvedilol/stent). Modest change in neointimal and lumen area was observed in 96 and 154 micrometer carvedilol/stent. A proliferating nuclear cell antigen-positive cells was noted 7.78 +/- 2.97% in 7 micrometer carvedilol/stent vs. 17.82 +/- 1.45% in 0 micrometer carvedilol/stent (p=0.0001).
CONCLUSION
A Low dose carvedilol stent coating produces a significant inhibition of neointimal hyperplasia in a porcine model of stent restenosis. This study provides a potential therapeutic benefit of carvedilol coating in the prevention of human stent restenosis.