Paclitaxel stent coating inhibits neointimal hyperplasia at 4 weeks in a porcine model of coronary restenosis

Background-Despite limiting elastic recoil and late vascular remodeling aft er angioplasty, coronary stents remain vulnerable to restenosis, caused pri marily by neointimal hyperplasia. Paclitaxel, a microtubule-stabilizing dru g, has been shown to inhibit vascular smooth muscle cell migration and prol iferation contributing to neointimal hyperplasia. We tested whether paclita xel-coated coronary stents are effective at preventing neointimal prolifera tion in a porcine model of restenosis. Methods and Results-Palmaz-Schatz stents were dip-coated with paclitaxel (0 , 0.2, 15, or 187 mug/stent) by immersion in ethanolic paclitaxel and evapo ration of the solvent. Stents were deployed with mild oversizing in the lef t anterior descending coronary artery (LAD) of 41 minipigs. The treatment e ffect was assessed 4 weeks after stent implantation. The angiographic late loss index (mean luminal diameter) decreased with increasing paclitaxel dos e (P<0.0028 by ANOVA), declining by 84.3% (from 0.352 to 0.055, P<0.05) at the highest level tested (187 mug/stent versus control). Accompanying this change, the neointimal area decreased (by 39.5%, high-dose versus control; P<0.05) with increasing dose (P<0.040 by ANOVA), whereas the luminal area i ncreased (by 90.4%, high-dose versus control; P<0.05) with escalating dose (P<0.0004 by ANOVA). Inflammatory cells were seen infrequently, and there w ere no cases of aneurysm or thrombosis. Conclusions-Paclitaxel-coated coronary stents produced a significant dose-d ependent inhibition of neointimal hyperplasia and luminal encroachment in t he pig LAD 28 days after implantation; later effects require further study. These results demonstrate the potential therapeutic benefit of paclitaxel- coated coronary stents in the prevention and treatment of human coronary re stenosis.