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REVASC - REVASC
Description:
Randomized trial of intramyocardial injection of AdVEGF121 for severe angina.
Hypothesis:
Treatment with intramyocardial injection of AdVEGF121 (Biobypass) will improve change in time to ST depression in patients with CCS class II-IV angina not controlled with maximal medication and not eligible for revascularization.
Study Design
Study Design:
Patients Enrolled: 67.
Mean Follow Up: 52 weeks.
Patient Populations:
CCS class II-IV angina; maximal medication therapy; not eligible for revascularization.
Primary Endpoints:
Change in time to 1 mm ST depression from baseline to 12 weeks on exercise treadmill test.
Secondary Endpoints:
Change in time to 1 mm ST depression from baseline to 26 weeks on exercise treadmill test; time to moderate angina, total exercise duration, and improvement of angina class, at 12 weeks and 26 weeks.
Drug/Procedures Used:
Patients were treated with intramyocardial injection of adenoviral vector containing VEGF121 (30 injections of 30 x 100 microL each) directly into the free wall of the left ventricle via a minithoracotomy versus standard therapy. Patients were stratified by number of coronary artery bypass grafts (CABGs) prior to randomization (<2 vs >=2 CABGs).
Principal Findings:
Baseline exercise testing toleranc (ETT) parameters were similar between the two groups (p=NS). More patients in the AdVEGF121 arm had diabetes (47% vs 23%), but other baseline characteristics were similar. Change in time to 1 mm ST depression from baseline on ETT was not improved at 12 weeks (p=0.356), but was improved at 26 weeks (p=0.024). Total exercise duration was improved at both 12 weeks (p=0.011) and 26 weeks (p=0.014), as was time to level 2 angina (p=0.006 at 12 weeks, p=0.002 at 26 weeks). On the Seattle Angina Questionnaire, the angina stability score, angina frequency score, and disease perception score were all improved from baseline to 6, 12, and 26 weeks in the AdVEGF arm (p<0.001 for each), but not in the medical care arm. There were no differences in serious adverse events in the 2 arms (n=10 in AdVEGF arm vs n=11 in control arm), as well as no difference in mortality (n=2 vs n=1, respectively).
Interpretation:
The REVASC trial is the first randomized trial to deliver angiogenic genes by direct intramyocardial injections. While the primary endpoint was not significant, many positive findings were reported with minimal serious adverse events. By design of the trial, patients and medical personnel were not blinded to therapy. Therefore, a placebo effect cannot be discounted. Given the late (26 week) improved time to ST depression and the improved exercise capacity and angina symptoms, a randomized blinded trial of this therapy in patients with no additional treatment options may be warranted. Clinical application for use of the therapy cannot be drawn from the present small randomized but nonblinded trial.
References:
Presented at AHA 2002, late breaking clinical trials.
Keywords: Placebo Effect, Vascular Endothelial Growth Factor A, Heart Failure, Surveys and Questionnaires, Coronary Artery Bypass, Heart Ventricles, Hirudins, Diabetes Mellitus, Exercise Test
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