Edifoligide and long-term outcomes after coronary artery bypass grafting: PRoject of Ex-vivo Vein graft ENgineering via Transfection IV (PREVENT IV) 5-year results

Am Heart J. 2012 Sep;164(3):379-386.e1. doi: 10.1016/j.ahj.2012.05.019.

Abstract

Background: Edifoligide, an E2F transcription factor decoy, does not prevent vein graft failure or adverse clinical outcomes at 1 year in patients undergoing coronary artery bypass grafting (CABG). We compared the 5-year clinical outcomes of patients in PREVENT IV treated with edifoligide and placebo to identify predictors of long-term clinical outcomes.

Methods: A total of 3,014 patients undergoing CABG with at least 2 planned vein grafts were enrolled. Kaplan-Meier curves were generated to compare the long-term effects of edifoligide and placebo. A Cox proportional hazards model was constructed to identify factors associated with 5-year post-CABG outcomes. The main outcome measures were death, myocardial infarction (MI), repeat revascularization, and rehospitalization through 5 years.

Results: Five-year follow-up was complete in 2,865 patients (95.1%). At 5 years, patients randomized to edifoligide and placebo had similar rates of death (11.7% and 10.7%, respectively), MI (2.3% and 3.2%), revascularization (14.1% and 13.9%), and rehospitalization (61.6% and 62.5%). The composite outcome of death, MI, or revascularization occurred at similar frequency in patients assigned to edifoligide and placebo (26.3% and 25.5%, respectively; hazard ratio 1.03 [95% CI 0.89-1.18], P = .721). Factors associated with death, MI, or revascularization at 5 years included peripheral and/or cerebrovascular disease, time on cardiopulmonary bypass, lung disease, diabetes mellitus, and congestive heart failure.

Conclusions: Up to a quarter of patients undergoing CABG will have a major cardiac event or repeat revascularization procedure within 5 years of surgery. Edifoligide does not affect outcomes after CABG; however, common identifiable baseline and procedural risk factors are associated with long-term outcomes after CABG.

Trial registration: ClinicalTrials.gov NCT00042081.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Combined Modality Therapy
  • Coronary Artery Bypass*
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / surgery*
  • Double-Blind Method
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Myocardial Infarction / epidemiology
  • Myocardial Revascularization / statistics & numerical data
  • Oligonucleotides / therapeutic use*
  • Patient Readmission / statistics & numerical data
  • Postoperative Complications*
  • Proportional Hazards Models
  • Treatment Outcome
  • Young Adult

Substances

  • Oligonucleotides
  • edifoligide

Associated data

  • ClinicalTrials.gov/NCT00042081