Elsevier

American Heart Journal

Volume 164, Issue 3, September 2012, Pages 379-386.e1
American Heart Journal

Clinical Investigation
Coronary Artery Disease
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

https://doi.org/10.1016/j.ahj.2012.05.019Get rights and content

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.

Section snippets

Study population

These analyses were conducted using the PRoject of Ex-vivo Vein graft ENgineering via Transfection IV (PREVENT IV) clinical trial database. Details of the PREVENT IV trial design have been published previously.10 In summary, PREVENT IV was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial of ex vivo treatment of vein grafts with edifoligide in patients undergoing primary isolated CABG with at least 2 planned vein grafts (ClinicalTrials.gov identifier, NCT00042081). The

Clinical follow-up

Five-year follow-up was complete in 95.1% of patients, including 94.8% in the edifoligide group and 95.3% in the placebo group. Consent for participation was withdrawn by 2.0% of enrolled patients (2.4% in the edifoligide group and 1.7% in the placebo groups), and 2.9% of patients were lost to follow-up (2.8% in the edifoligide group and 3.1% in the placebo group). Figure 1 displays the flow of patients through the trial.

Demographic and operative characteristics

Baseline demographic and operative characteristics of the PREVENT IV

Discussion

Although edifoligide exhibited a trend toward improved clinical outcomes at 1 year of follow-up,3 the agent does not have delayed beneficial effects on 5-year clinical outcomes after CABG surgery. In this contemporary CABG surgery population, major adverse cardiac events continued to occur at similar rates for patients in both arms of the trial. Multivariable models revealed several important baseline variables associated with death and other clinical end points at 5 years.

The results of

Conclusions

Up to a quarter of patients undergoing CABG surgery will have a major cardiac event or repeat revascularization procedure within 5 years of surgery. Edifoligide had no effect on clinical outcomes through 5 years after CABG surgery. Common identifiable baseline and procedural risk factors are associated with subsequent clinical events after CABG surgery.

Disclosures

This work was supported internally by the Duke Clinical Research Institute. Dr Williams is supported by training grant T32-HL069749 from the National Institutes of Health (NIH). Mr Reyes is supported by NIH grant T32-HL079896. Drs Williams, Ferguson, Mack, and Alexander are supported, in part, by grant U01-HL088953 from the NIH Cardiothoracic Surgical Trials Network submission. Complete listings of Dr Lopes', Dr Mehta's, Dr Peterson's, Dr Harrington's, Dr Califf's, and Dr Alexander's

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