title: Paclitaxel stent coating inhibits neointimal hyperplasia at 4 weeks in a porcine model of coronary restenosis.
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.
  
  
  RESULTS
  Palmaz-Schatz stents were dip-coated with paclitaxel (0, 0.2, 15, or 187 microgram/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 microgram/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.
authors.affiliation: Division of Cardiology, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Md, USA. aheldman@jhmi.edu
authors.forename: A W
authors.initials: AW
authors.lastname: Heldman
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.forename: G M
authors.initials: GM
authors.lastname: Jenkins
authors.forename: P F
authors.initials: PF
authors.lastname: Heller
authors.forename: D W
authors.initials: DW
authors.lastname: Kim
authors.forename: M
authors.initials: M
authors.lastname: Ware
authors.forename: C
authors.initials: C
authors.lastname: Nater
authors.forename: R H
authors.initials: RH
authors.lastname: Hruban
authors.forename: B
authors.initials: B
authors.lastname: Rezai
authors.forename: B S
authors.initials: BS
authors.lastname: Abella
authors.forename: K E
authors.initials: KE
authors.lastname: Bunge
authors.forename: J L
authors.initials: JL
authors.lastname: Kinsella
authors.forename: S J
authors.initials: SJ
authors.lastname: Sollott
authors.forename: E G
authors.initials: EG
authors.lastname: Lakatta
authors.forename: J A
authors.initials: JA
authors.lastname: Brinker
authors.forename: W L
authors.initials: WL
authors.lastname: Hunter
authors.forename: J P
authors.initials: JP
authors.lastname: Froehlich
mesh_terms: D000818:Animals; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000737:chemistry / Q000187:drug effects* / Q000601:surgery; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006083:Graft Occlusion, Vascular / Q000473:pathology / Q000517:prevention & control*; D006965:Hyperplasia / Q000473:pathology / Q000517:prevention & control; D015918:Infusion Pumps, Implantable; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage* / Q000032:analysis; D015607:Stents; D013499:Surface Properties; D013556:Swine, Miniature; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology / Q000601:surgery
chemical_list: D017239:Paclitaxel