Stent-based delivery of sirolimus reduces neointimal formation in a porcine coronary model

Background-The purpose of this study was to determine the efficacy of stent -based delivery of sirolimus (SRL) alone or in combination with dexamethaso ne (DEX) to reduce in-stent neointimal hyperplasia. SRL is a potent immunos uppressive agent that inhibits SMC proliferation by blocking cell cycle pro gression. Methods and Results-Stents were coated with a nonerodable polymer containin g 185 mug SRL, 350 mug DEX, or 185 mug SRL and 350 mug DEX. Polymer biocomp atibility 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 mug at 3 days. At 7 days, proliferating cell nuclear antigen and retinobla stoma protein expression were reduced 60% and 50%, respectively, by the SRL stents. After 28 days, the mean neointimal area was 2.47+/-1.04 mm(2) for the SRL alone and 2.42+/-1.04 mm(2) for the combination of SRL and DEX comp ared with the metal (5.06+/-1.88 mm(2), P<0.0001) or DEX-coated stents (4.3 1+/-3.21 mm(2), 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 inhibi ting cellular proliferation.