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

Alan W. Heldman, Linda Cheng, G. Mark Jenkins, Phillip F. Heller, Dong Woon Kim, Melvin Ware, Cynthia Nater, Ralph H. Hruban, Banafsheh Rezai, Benjamin S. Abella, Katherine E. Bunge, James L. Kinsella, Steven J. Sollott, Edward G. Lakatta, Jeffrey A. Brinker, William L. Hunter, Jeffrey P. Froehlich

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364 Scopus citations

Abstract

Background - Despite limiting elastic recoil and late vascular remodeling after angioplasty, coronary stents remain vulnerable to restenosis, caused primarily by neointimal hyperplasia. Paclitaxel, a microtubule-stabilizing drug, has been shown to inhibit vascular smooth muscle cell migration and proliferation contributing to neointimal hyperplasia. We tested whether paclitaxel-coated coronary stents are effective at preventing neointimal proliferation in a porcine model of restenosis. Methods and Results - Palmaz-Schatz stents were dip-coated with paclitaxel (0, 0.2, 15, or 187 μg/stent) by immersion in ethanolic paclitaxel and evaporation of the solvent. Stents were deployed with mild oversizing in the left anterior descending coronary artery (LAD) of 41 minipigs. The treatment effect was assessed 4 weeks after stent implantation. The angiographic late loss index (mean luminal diameter) decreased with increasing paclitaxel dose (P<0.0028 by ANOVA), declining by 84.3% (from 0.352 to 0.055, P<0.05) at the highest level tested (187 μg/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 increased (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 were no cases of aneurysm or thrombosis. Conclusions - Paclitaxel-coated coronary stents produced a significant dose-dependent inhibition of neointimal hyperplasia and luminal encroachment in the 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 restenosis.

Original languageEnglish (US)
Pages (from-to)2289-2295
Number of pages7
JournalCirculation
Volume103
Issue number18
DOIs
StatePublished - May 8 2001

Keywords

  • Angioplasty
  • Paclitaxel
  • Restenosis
  • Stents

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Heldman, A. W., Cheng, L., Jenkins, G. M., Heller, P. F., Kim, D. W., Ware, M., Nater, C., Hruban, R. H., Rezai, B., Abella, B. S., Bunge, K. E., Kinsella, J. L., Sollott, S. J., Lakatta, E. G., Brinker, J. A., Hunter, W. L., & Froehlich, J. P. (2001). Paclitaxel stent coating inhibits neointimal hyperplasia at 4 weeks in a porcine model of coronary restenosis. Circulation, 103(18), 2289-2295. https://doi.org/10.1161/01.CIR.103.18.2289