Background— The purpose of this study was to determine the efficacy of stent-based delivery of sirolimus (SRL) alone or in combination with dexamethasone (DEX) to reduce in-stent neointimal hyperplasia. SRL is a potent immunosuppressive agent that inhibits SMC proliferation by blocking cell cycle progression.

Methods and Results— Stents were coated with a nonerodable polymer containing 185 μg SRL, 350 μg DEX, or 185 μg SRL and 350 μg DEX. Polymer biocompatibility studies in the porcine and canine models showed acceptable tissue response at 60 days. Forty-seven stents (metal, n=13; SRL, n=13; DEX, n=13; SRL and DEX, n=8) were implanted in the coronary arteries of 16 pigs. The tissue level of SRL was 97±13 ng/artery, with a stent content of 71±10 μg at 3 days. At 7 days, proliferating cell nuclear antigen and retinoblastoma protein expression were reduced 60% and 50%, respectively, by the SRL stents. After 28 days, the mean neointimal area was 2.47±1.04 mm² for the SRL alone and 2.42±1.04 mm² for the combination of SRL and DEX compared with the metal (5.06±1.88 mm², P<0.0001) or DEX-coated stents (4.31±3.21 mm², P<0.001), resulting in a 50% reduction of percent in-stent stenosis.

Conclusions— Stent-based delivery of SRL via a nonerodable polymer matrix is feasible and effectively reduces in-stent neointimal hyperplasia by inhibiting cellular proliferation.