title: Experimental evaluation of efficacy and healing response of everolimus-eluting stents in the familial hypercholesterolemic swine model: a comparative study of bioabsorbable versus durable polymer stent platforms.
abstract: BACKGROUND
  The utility of animal models for the prediction of drug-eluting stent (DES) efficacy in human clinical trials is still unclear. The familial hypercholesterolemic swine (FHS) model has been shown to induce a human-like neointimal response to bare metal stent (BMS) implantation. However, its utility to discriminate efficacy signals following DES implantation is unknown. In this study, we aimed to test the efficacy and healing response of several everolimus-eluting stent (EES) platforms in the coronary territory of the FHS.
  
  
  METHODS
  A total of 19 EES platforms (SYNERGY=6, SYNERGY½-dose=7, and PROMUS Element=6) and an identical BMS control (Element=6) were implanted into the coronary arteries of nine FHS. All implants were performed under intravascular ultrasound guidance using a 1.2 : 1 overstretch ratio. At 30 days, the vascular response to the implant was evaluated by quantitative coronary angiography, optical coherence tomography, and histology.
  
  
  RESULTS
  At 28 days, all EES platforms showed a significant decrease in angiographic late lumen loss (between 27 and 37%) compared with the BMS control group. This finding was confirmed both by optical coherence tomography (mean neointimal thickness=28-42% reduction) and by histology (mean neointimal thickness=44-55% reduction). All EES platforms showed similar degrees of neointimal inhibition. The presence of moderate to severe para-strut inflammation was observed in 83% of the stent sections in the BMS group compared with 28.6% in the SYNERGY½-dose group and 0% in the SYNERGY and PROMUS groups (P=0.0002). There was a 68-95% reduction in MMP9 expression in the media in all EES platforms compared with the BMS controls. The presence of mild to moderate para-strut fibrin deposits ranged from 66.7 to 83.4% in all EES platforms compared with 16.7% in the EBMS group.
  
  
  CONCLUSIONS
  The FHS coronary injury model showed the efficacy of several EES platforms compared with an identical BMS control. Everolimus eluted from different polymeric platforms showed lower levels of inflammation and slightly higher fibrin deposits compared with BMS controls.
authors.affiliation: aSkirball Center for Cardiovascular Research at Cardiovascular Research Foundation, Orangeburg bColumbia University Medical Center, New York, New York cBoston Scientific Corporation, Natick, Massachusetts dDepartment of Animal Sciences, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Armando
authors.initials: A
authors.lastname: Tellez
authors.forename: Paul S
authors.initials: PS
authors.lastname: Seifert
authors.forename: Elina
authors.initials: E
authors.lastname: Donskoy
authors.forename: Natalia
authors.initials: N
authors.lastname: Sushkova
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Pennington
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Milewski
authors.forename: Christian G
authors.initials: CG
authors.lastname: Krueger
authors.forename: Greg L
authors.initials: GL
authors.lastname: Kaluza
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Eppihimer
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Huibregtse
authors.forename: Keith D
authors.initials: KD
authors.lastname: Dawkins
authors.forename: Juan F
authors.initials: JF
authors.lastname: Granada
mesh_terms: D000818:Animals; D019917:Blood Vessel Prosthesis Implantation / Q000379:methods; D017023:Coronary Angiography / Q000379:methods; D003331:Coronary Vessels / Q000473:pathology*; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents / Q000009:adverse effects / Q000592:standards; D000068338:Everolimus; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000628:therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D008955:Models, Cardiovascular; D058426:Neointima / Q000175:diagnosis / Q000209:etiology; D011108:Polymers / Q000494:pharmacology; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D013552:Swine; D041623:Tomography, Optical Coherence / Q000379:methods; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional / Q000379:methods
chemical_list: D007166:Immunosuppressive Agents; D011108:Polymers; D000068338:Everolimus; D020123:Sirolimus