title: Lowering the dose of sirolimus, released from a nonpolymeric hydroxyapatite coated coronary stent, reduces signs of delayed healing.
abstract: OBJECTIVE
  The aim of this study was to compare efficacy of low- and high-dose sirolimus release (25, 40, or 100 microg) from hydroxyapatite (HAp) with Cypher (Cordis, Johnson & Johnson, Warren, New Jersey) (111 microg sirolimus) in porcine coronary arteries.
  
  
  BACKGROUND
  Polymer-based sirolimus-eluting stents such as Cypher interfere with vascular healing, probably due to the permanent presence of the polymer coating and the high sirolimus dose. The use of low-dose sirolimus and inert nonpolymeric but biodegradable coatings such as HAp might be more appropriate.
  
  
  METHODS
  Stents (n = 68) were implanted, guided by quantitative coronary angiography. All swine received clopidogrel and acetylsalicylic acid during 28 days follow-up. Safety of the coating in absence of drugs was studied by comparing HAp with and without a lipid-based release regulating layer (HApR) with bare-metal stents. Efficacy was studied by comparing the release of 25, 40, and 100 microg sirolimus with Cypher.
  
  
  RESULTS
  The safety study (without drug) revealed no differences in neointimal thickening in response to HAp and HApR with complete healing in all groups. Dose response analysis showed that neointimal thickening was similar in all groups regardless of sirolimus dose, with a normal appearance of the endothelium. There was, however, a dose-dependent increase in fibrinoid (p = 0.028), considered to be a marker of delayed healing. The Cypher stent induced the highest amount of fibrinoid.
  
  
  CONCLUSIONS
  Reducing the dose of sirolimus eluting from a biocompatible HAp coated stent reduces signs of delayed vascular healing, without affecting neointimal hyperplasia.
authors.affiliation: Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Wim J
authors.initials: WJ
authors.lastname: van der Giessen
authors.forename: Oana
authors.initials: O
authors.lastname: Sorop
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Serruys
authors.forename: Ilona
authors.initials: I
authors.lastname: Peters-Krabbendam
authors.forename: Heleen M M
authors.initials: HM
authors.lastname: van Beusekom
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation*; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D000077144:Clopidogrel; D020099:Coated Materials, Biocompatible; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000209:etiology / Q000517:prevention & control; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D054855:Drug-Eluting Stents; D017886:Durapatite / Q000737:chemistry* / Q000633:toxicity; D006965:Hyperplasia; D008055:Lipids / Q000737:chemistry; D008422:Materials Testing; D023421:Models, Animal; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011474:Prosthesis Design; D020123:Sirolimus / Q000008:administration & dosage*; D013193:Stainless Steel; D013499:Surface Properties; D034421:Sus scrofa; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D002317:Cardiovascular Agents; D020099:Coated Materials, Biocompatible; D008055:Lipids; D010975:Platelet Aggregation Inhibitors; D013193:Stainless Steel; D017886:Durapatite; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin; D020123:Sirolimus