Long-Term Effects of Novel Biodegradable, Polymer-Coated, Sirolimus-Eluting Stents on Neointimal Formation in a Porcine Coronary Model

The postulated relationship between nonbiodegradable polymers and late stent thrombosis has led to a concerted effort to seek alternative biodegradable polymers for drug delivery. The purpose of this study was to evaluate the long-term effects of novel sirolimus-eluting stents (SES) with biodegradable polylactic-co-glycolic acid (PLGA) polymer on neointimal thickening in a porcine coronary model. Three types of stents were implanted in different coronary arteries of the same mini-swine: bare cobalt-chromium stents (BMS); PLGA-coated-only stents (PCOS); and PLGA-coated, sirolimus-eluting stents (PCSES). A total of 26 animals underwent successful placement of 78 oversized stents (each stent-group, n = 26) in the coronary arteries with histopathologic analysis and Western blot at 28 days, 3 months, or 1 year. At 28 days and 3 months, the mean neointimal area was about two-fold lower in PCSES versus BMS or PCOS. At 1 year, the mean intimal area was similar for PCSES (1.76 +/- 0.28 mm(2)) and BMS (2.06 +/- 0.23 mm(2), P = 0.051). Western blot analysis demonstrated decreased expression of p27(kip1) in the vessel wall 3 months after PCSES implantation as compared with 28 days. PCSES effectively reduced in-stent neointimal formation for the first 3 months in this porcine coronary model. Beyond 3 months, neointimal proliferation was not substantially inhibited by PCSES. The observed delayed neointimal hyperplasia with PCSES may be partly related to the potential side effects of sirolimus and/or late insufficient arterial drug levels.