title: The effect of variable release kinetics on Paclitaxel efficacy from a drug eluting stent in a porcine model.
abstract: OBJECTIVE
  Paclitaxel is a potent and effective inhibitor of neointimal proliferation after coronary stenting. The Conor stent loaded with Paclitaxel can be programmed with multi-parameter matrix of dose, temporal release profiles and release pathways. The aim of this study was to determine the most efficacious dose and release pattern of Paclitaxel in a porcine model and parallels the PISCES trial.
  
  
  METHODS
  32 farm pigs were implanted with Conor stents loaded with 10 or 30 microg of Paclitaxel with, 10 or 30 day and mural or bidirectional release patterns. Angiographic and histomorphometric analysis was -performed at 30 and 90 days.
  
  
  RESULTS
  All doses of Paclitaxel were angiographically superior to control (P < 0.01). At 30 days, intimal thickness was similar between Pisces D4 (30 microg/10 days, bidirectional release), D5 (10 microg/30 day mural) and D6 (30 microg/30 day, mural) with D4 having the lowest intimal thickness (167+/-59 microm). There was a significant increase in the mural injury associated with D4 in comparison to all other doses (P < 0.00001). At 90 days D4 was significantly worse in comparison to Pisces D5 and D6; (P < 0.01) and Pisces D5 and D6 were similar to controls.
  
  
  CONCLUSIONS
  10 day release of Paclitaxel may be too short a period to inhibit neointimal proliferation after coronary stenting, or the rapid release of Paclitaxel may induce chemical injury causing secondary insult to the artery resulting in a rebound increase in intimal thickness at 90 days. These data parallel clinical findings in the PISCES trial.
authors.affiliation: Cardiovascular Intervention Center, Cedars Sinai Medical Center Los Angeles Ca, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Aragon
authors.forename: Saibal
authors.initials: S
authors.lastname: Kar
authors.forename: Fermin
authors.initials: F
authors.lastname: Tio
authors.forename: Brett
authors.initials: B
authors.lastname: Trauthen
authors.forename: Alexander
authors.initials: A
authors.lastname: Parisky
authors.forename: Colin
authors.initials: C
authors.lastname: Watanabe
authors.forename: Aamer
authors.initials: A
authors.lastname: Jamali
authors.forename: Neal
authors.initials: N
authors.lastname: Eigler
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Serruys
authors.forename: Frank
authors.initials: F
authors.lastname: Litvack