Clinical InvestigationCoronary Artery DiseaseEdifoligide and long-term outcomes after coronary artery bypass grafting: PRoject of Ex-vivo Vein graft ENgineering via Transfection IV (PREVENT IV) 5-year results
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 Consent for participation was withdrawn by 2.0% of enrolled patients (2.4% in the edifoligide group and 1.7% in the placebo groups), and 2.9% of patients were lost to follow-up (2.8% in the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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2019, Drug Discovery TodayCitation Excerpt :The E2F-1 decoy had no effect on the primary end point (death or vein graft stenosis) or on any secondary end point (incidence of major adverse cardiac events) [126]. Follow-up of 2865 of the 3014 patients [126] for 5 years suggested that the E2F-1 decoy had the same effects (rates of death, myocardial infarction, revascularization, and rehospitalization) as the placebo [127]. Limitations of conventional therapies for atherosclerosis have led to extensive investigations to find novel drugs.
Antithrombotic Therapy Following CABG: For the Patient, Not the Bypass Graft<sup>∗</sup>
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Clinicaltrials.gov Identifier; NCT00042081.
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Dr Lorenz is now at Portola Pharmaceuticals, San Francisco, CA.