edifoligide and Postoperative-Complications

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.. 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.. 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.. 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.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Coronary Artery Bypass; Coronary Artery Disease; Double-Blind Method; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Oligonucleotides; Patient Readmission; Postoperative Complications; Proportional Hazards Models; Treatment Outcome; Young Adult

Coronary artery bypass graft (CABG) surgery with autologous vein graft (VG) conduit is one of the most frequently performed operations in the United States. Unfortunately, many VGs become occluded during long-term follow-up largely because of neointimal hyperplasia. A novel approach to preventing neointimal hyperplasia is with the double-stranded oligonucleotide edifoligide (Corgentech Inc, South San Francisco, Calif). Edifoligide inhibits E2F, a transcription factor that activates cell-cycle genes responsible for neointimal hyperplasia.. PREVENT IV is a phase-III, multicenter, randomized double-blind placebo-controlled trial of ex vivo treatment of autologous VGs with edifoligide in patients undergoing initial CABG surgery. The primary end point is VG failure, defined as death or > or =75% stenosis in a treated VG at 12- to 18-month angiographic follow-up. Secondary end points include major adverse cardiac events through at least 5 years and adverse events through 30 days.. Enrollment of 3014 patients from 107 sites was completed on October 22, 2003. The baseline and procedural characteristics of the PREVENT IV population are generally well matched to a contemporary population of patients undergoing initial CABG from the Society of Thoracic Surgeons National Database. Angiographic follow-up is ongoing and scheduled to be completed in March 2005.. The PREVENT IV data will establish whether VG pretreatment with an E2F transcription factor decoy, edifoligide, can improve graft patency and reduce the long-term morbidity and mortality of patients undergoing CABG surgery.

Topics: Aged; Coronary Artery Bypass; DNA; Equipment Design; Female; Follow-Up Studies; Humans; Hyperplasia; Injections, Intravenous; Male; Middle Aged; Multicenter Studies as Topic; Oligonucleotides; Postoperative Complications; Randomized Controlled Trials as Topic; Research Design; Tunica Intima