Morphology after coronary stenting demonstrates early thrombus formation and acute inflammation followed by neointimal growth. Medial injury and lipid core penetration by struts result in increased inflammation. Neointima increases as the ratio of stent area to reference lumen area increases. Deployment strategies that reduce medial damage and avoid stent oversizing may lower the frequency of in-stent restenosis.

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 g SRL, 350 g DEX, or 185 g SRL and 350 g DEX. Polymer biocompatibility studies in the porcine and canine models showed acceptable tissue response at 60 days. Forty-seven stents (metal, nϭ13; SRL, nϭ13; DEX, nϭ13; SRL and DEX, nϭ8) were implanted in the coronary arteries of 16 pigs. The tissue level of SRL was 97Ϯ13 ng/artery, with a stent content of 71Ϯ10 g 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 2.47Ϯ1.04 mm 2 for the SRL alone and 2.42Ϯ1.04 mm 2 for the combination of SRL and DEX compared with the metal (5.06Ϯ1.88 mm 2 , PϽ0.0001) or DEX-coated stents (4.31Ϯ3.21 mm 2 , PϽ0.001), 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.

Background-Paclitaxel can inhibit vascular smooth muscle proliferation in vitro, and early studies suggest that paclitaxel may be useful in preventing restenosis.