title: Efficacy and safety of edifoligide, an E2F transcription factor decoy, for prevention of vein graft failure following coronary artery bypass graft surgery: PREVENT IV: a randomized controlled trial.
abstract: BACKGROUND
  Coronary artery bypass graft (CABG) surgery with autologous vein grafting is commonly performed. Progressive neointimal hyperplasia, however, contributes to considerable vein graft failure. Edifoligide is an oligonucleotide decoy that binds to and inhibits E2F transcription factors and thus may prevent neointimal hyperplasia and vein graft failure.
  
  
  OBJECTIVE
  To assess the efficacy and safety of pretreating vein grafts with edifoligide for patients undergoing CABG surgery.
  
  
  METHODS
  A phase 3 randomized, double-blind, placebo-controlled trial of 3014 patients undergoing primary CABG surgery with at least 2 planned saphenous vein grafts and without concomitant valve surgery, who were enrolled between August 2002 and October 2003 at 107 US sites.
  
  
  METHODS
  Vein grafts were treated ex vivo with either edifoligide or placebo in a pressure-mediated delivery system. The first 2400 patients enrolled were scheduled for 12- to 18-month follow-up angiography.
  
  
  METHODS
  The primary efficacy end point was angiographic vein graft failure (> or =75% vein graft stenosis) occurring 12 to 18 months after CABG surgery. Other end points included other angiographic variables, adverse events through 30 days, and major adverse cardiac events.
  
  
  RESULTS
  A total of 1920 patients (80%) either died (n = 91) or underwent follow-up angiography (n = 1829). Edifoligide had no effect on the primary end point of per patient vein graft failure (436 [45.2%] of 965 patients in the edifoligide group vs 442 [46.3%] of 955 patients in the placebo group; odds ratio, 0.96 [95% confidence interval {CI}, 0.80-1.14]; P = .66), on any secondary angiographic end point, or on the incidence of major adverse cardiac events at 1 year (101 [6.7%] of 1508 patients in the edifoligide group vs 121 [8.1%] of 1506 patients in the placebo group; hazard ratio, 0.83 [95% CI, 0.64-1.08]; P = .16).
  
  
  CONCLUSIONS
  Failure of at least 1 vein graft is quite common within 12 to 18 months after CABG surgery. Edifoligide is no more effective than placebo in preventing these events. Longer-term follow-up and additional research are needed to determine whether edifoligide has delayed beneficial effects, to understand the mechanisms and clinical consequences of vein graft failure, and to improve the durability of CABG surgery. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT00042081.
authors.affiliation: Duke University Medical Center, Duke Clinical Research Institute, Durham, NC 27715, USA. john.h.alexander@duke.edu
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.forename: Gail
authors.initials: G
authors.lastname: Hafley
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Eric D
authors.initials: ED
authors.lastname: Peterson
authors.forename: T Bruce
authors.initials: TB
authors.lastname: Ferguson
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Lorenz
authors.forename: Abhinav
authors.initials: A
authors.lastname: Goyal
authors.forename: Michael
authors.initials: M
authors.lastname: Gibson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mack
authors.forename: Daniel
authors.initials: D
authors.lastname: Gennevois
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Kouchoukos
mesh_terms: D000368:Aged; D000792:Angiography; D001026:Coronary Artery Bypass; D004247:DNA / Q000627:therapeutic use*; D004311:Double-Blind Method; D050684:E2F Transcription Factors; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000627:therapeutic use*; D012501:Saphenous Vein / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology / Q000637:transplantation*; D016019:Survival Analysis; D020858:Tissue and Organ Harvesting; D014162:Transfection; D014182:Transplantation, Autologous; D019737:Transplants; D014654:Vascular Patency / Q000187:drug effects*
chemical_list: D050684:E2F Transcription Factors; D009841:Oligonucleotides; C502518:edifoligide; D004247:DNA