title: Preclinical evaluation of second-generation everolimus- and zotarolimus-eluting coronary stents.
abstract: OBJECTIVE
  This study was designed to evaluate the pharmacokinetic and vascular healing of a second-generation everolimus-eluting stent (EES) and slow-release zotarolimus-eluting stent (R-ZES).
  
  
  BACKGROUND
  Second-generation DESs have alleviated the safety concerns of late stent thrombosis by addressing issues of polymer biocompatibility and stent design, and optimizing drug loads and release kinetics. No preclinical comparison study exists between these stents.
  
  
  METHODS
  Rabbit iliac artery stent implantation was performed using Xience Prime EES and Resolute R-ZES. Histomorphometric evaluation was performed at 28 and 60 days after implantation in an induced atheroma model. Endothelial coverage and maturation were assessed by scanning electron microscopy and immuno-labeling at 14 and 28 days following deployment. For pharmacokinetic studies, arterial tissue and stents were retrieved at 3, 14, 28, and 90 days, and blood samples were obtained during the first 24 hours.
  
  
  RESULTS
  Vascular remodeling (percent stenosis, neointimal thickness) was similar in arteries implanted with either stent group. At 28 days, inflammation was significantly less in the EES group as compared to the R-ZES group (inflammation score: 1.59 ± 0.52 vs 2.22 ± 0.69, respectively; P=.044), with no differences observed at 60 days. Endothelial coverage was similar between both groups; however, endothelial maturation above stent struts was significantly higher in the EES group vs R-ZES group at 28 days (33 ± 20% vs 22 ± 21%, respectively; P=.040). Arterial drug level concentrations were also shown to be significantly less in the EES group vs the R-ZES group (P<.0001).
  
  
  CONCLUSIONS
  Overall, EES and R-ZES displayed similar remodeling properties with lower arterial drug levels observed in the EES group vs the R-ZES group, which may have led to more rapid endothelial maturation.
authors.affiliation: CVPath Institute Inc, Gaithersburg, Maryland 20878, USA.
authors.forename: Saami K
authors.initials: SK
authors.lastname: Yazdani
authors.forename: Alexander
authors.initials: A
authors.lastname: Sheehy
authors.forename: Masataka
authors.initials: M
authors.lastname: Nakano
authors.forename: Gaku
authors.initials: G
authors.lastname: Nakazawa
authors.forename: Marc
authors.initials: M
authors.lastname: Vorpahl
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Otsuka
authors.forename: Rosy S
authors.initials: RS
authors.lastname: Donn
authors.forename: Laura E
authors.initials: LE
authors.lastname: Perkins
authors.forename: Charles A
authors.initials: CA
authors.lastname: Simonton
authors.forename: Frank D
authors.initials: FD
authors.lastname: Kolodgie
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents; D004730:Endothelium, Vascular / Q000473:pathology / Q000648:ultrastructure; D000068338:Everolimus; D005263:Femoral Artery / Q000473:pathology / Q000648:ultrastructure; D007083:Iliac Artery / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D058226:Plaque, Atherosclerotic / Q000473:pathology* / Q000628:therapy* / Q000648:ultrastructure; D011817:Rabbits; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000068338:Everolimus; C489443:zotarolimus; D020123:Sirolimus