EXPERIMENTAL STUDY
Neointimal thickening after stent delivery of paclitaxel: change in composition and arrest of growth over six months
Douglas E. Drachman, MD*,
Elazer R. Edelman, MD, PhD, FACC*  ,
Philip Seifert, MS,
Adam R. Groothuis, MS,
Danielle A. Bornstein, BS,
Kalpana R. Kamath, PhD ,
Maria Palasis, PhD,
Dachuan Yang, PhD,
Sepideh H. Nott, ScM and
Campbell Rogers, MD, FACC*
* Department of Medicine, (Cardiac Catheterization Laboratory and Coronary Care Unit, Cardiovascular Division, Brigham and Women’s Hospital) Harvard Medical School, Boston, Massachusetts, USA
Harvard-M.I.T. Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
Boston Scientific Corporation, Natick, Massachusetts, USA
Manuscript received March 3, 2000;
revised manuscript received June 23, 2000,
accepted August 7, 2000.
Reprint requests and correspondence: Dr. Douglas E. Drachman, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115
ddrachman{at}partners.org
OBJECTIVES
The purpose of this study was to determine long-term effects of stent-based paclitaxel delivery on amount, rate and composition of neointimal thickening after stent implantation.
BACKGROUND
Paclitaxel prevents vascular smooth muscle cell proliferation and migration in vitro and in vivo. These actions, coupled with low solubility, make it a viable candidate for modulating vascular responses to injury and prolonged effects after local delivery. We asked whether local delivery of paclitaxel for a period of weeks from a stent coated with a bioerodible polymer could produce a sustained reduction in neointimal hyperplasia for up to six months after stenting.
METHODS
Stainless steel stents were implanted in the iliac arteries of rabbits after endothelial denudation. Stents were uncoated or coated with a thin layer of poly(lactide-co- -caprolactone) copolymer alone or containing paclitaxel, 200 µg.
RESULTS
Paclitaxel release in vitro followed first-order kinetics for two months. Tissue responses were examined 7, 28, 56 or 180 days after implantation. Paclitaxel reduced intimal and medial cell proliferation three-fold seven days after stenting and virtually eliminated later intimal thickening. Six months after stenting, long after drug release and polymer degradation were likely complete, neointimal area was two-fold lower in paclitaxel-releasing stents. Tissue responses in paclitaxel-treated vessels included incomplete healing, few smooth muscle cells, late persistence of macrophages and dense fibrin with little collagen.
CONCLUSIONS
Poly(lactide-co--caprolactone) copolymer-coated stents permit sustained paclitaxel delivery in a manner that virtually abolishes neointimal hyperplasia for months after stent implantation, long after likely completion of drug delivery and polymer degradation.
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Abbreviations and Acronyms
| | BrdU | = bromodeoxyuridine | | pLA/pCL | = poly(lactide-co--caprolactone) copolymer | | SMC | = smooth muscle cell | | vWF | = von Willebrand’s factor |
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