title: Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk.
abstract: OBJECTIVE
  This study examined human drug-eluting stents (DES) to determine the long-term effects of these stents on coronary arterial healing and identified mechanisms underlying late stent thrombosis (LST).
  
  
  BACKGROUND
  Although DES reduce the need for repeat revascularization compared with bare-metal stents (BMS), data suggest the window of thrombotic risk for Cypher (Cordis Corp., Miami Lakes, Florida) and Taxus (Boston Scientific Corp., Natick, Massachusetts) DES extends far beyond that for BMS.
  
  
  METHODS
  From a registry of 40 autopsies of DES (68 stents), 23 DES cases of >30 days duration were compared with 25 matched autopsies of BMS implantation. Late stent thrombosis was defined as an acute thrombus within a stent >30 days old.
  
  
  RESULTS
  Of 23 patients with DES >30 days old, 14 had evidence of LST. Cypher and Taxus DES showed greater delayed healing characterized by persistent fibrin deposition (fibrin score 2.3 +/- 1.1 vs. 0.9 +/- 0.8, p = 0.0001) and poorer endothelialization (55.8 +/- 26.5%) compared with BMS (89.8 +/- 20.9, p = 0.0001). Moreover, DES with LST showed more delayed healing compared with patent DES. In 5 of 14 patients suffering LST, antiplatelet therapy had been withdrawn. Additional procedural and pathologic risk factors for LST were: 1) local hypersensitivity reaction; 2) ostial and/or bifurcation stenting; 3) malapposition/incomplete apposition; 4) restenosis; and 5) strut penetration into a necrotic core.
  
  
  CONCLUSIONS
  The Cypher and Taxus DES result in delayed arterial healing when compared with BMS of similar implant duration. The cause of DES LST is multifactorial with delayed healing in combination with other clinical and procedural risk factors playing a role.
authors.affiliation: CVPath, International Registry of Pathology, Gaithersburg, Maryland 20878, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Joner
authors.forename: Aloke V
authors.initials: AV
authors.lastname: Finn
authors.forename: Andrew
authors.initials: A
authors.lastname: Farb
authors.forename: Erik K
authors.initials: EK
authors.lastname: Mont
authors.forename: Frank D
authors.initials: FD
authors.lastname: Kolodgie
authors.forename: Elena
authors.initials: E
authors.lastname: Ladich
authors.forename: Robert
authors.initials: R
authors.lastname: Kutys
authors.forename: Kristi
authors.initials: K
authors.lastname: Skorija
authors.forename: Herman K
authors.initials: HK
authors.lastname: Gold
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
mesh_terms: D000328:Adult; D000368:Aged; D023903:Coronary Restenosis; D003328:Coronary Thrombosis / Q000209:etiology* / Q000401:mortality; D003331:Coronary Vessels / Q000473:pathology*; D016757:Death, Sudden, Cardiac; D005260:Female; D006801:Humans; D008297:Male; D008670:Metals; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality; D017239:Paclitaxel; D020123:Sirolimus; D015607:Stents / Q000009:adverse effects*; D014945:Wound Healing
chemical_list: D008670:Metals; D017239:Paclitaxel; D020123:Sirolimus