Abstract 15235: High-Dose Plasmid VEGF Gene Transfer in Patients with Severe Coronary Artery Disease: Final Results of the First Latin American Trial of Gene Therapy in Myocardial Ischemia
We have shown that high dose intramyocardial injection of a plasmid coding VEGF165 (pVEGF) in pig and sheep models of myocardial ischemia induces angio-arteriogenesis and cardiomyogenesis with no side effects. We thus conducted a Phase I, open-label, uncontrolled trial to assess safety (primarily) and efficacy (secondarily) of pVEGF gene transfer in patients with severe coronary artery disease not amenable for conventional revascularization (PCI and/or CABG).
Methods: Ten patients with stable chronic angina despite maximal medication, myocardial ischemia and/or viability and rest ejection fraction (EF%) ≥ 30%, with negative screening for cancer (American Cancer Society) and proliferative retinopathy, received 3.8 mg of pVEGF distributed in ischemic regions with an intramyocardial injection catéter (MyoCath®). Statistical analysis: Wilcoxon Rank Test.
Results: No serious adverse events related to pVEGF or the catheter were observed at 6 or 24 months follow up (n=10). The Table shows baseline versus 6- and 24-months values for angina functional class (CCS-FC), Seattle Angina Questionnaire for quality of life (SAQ%), summed difference score (SDS) of myocardial perfusion (99mTc-sestamibi SPECT) and EF% under dobutamine stress echocardiography (Table). Plasma VEGF protein (ELISA) increased from 152.3±38.2 pg/mL to 371.1±80.5 pg/mL (p<0.05) at ten days after injection.
Conclusion: pVEGF gene transfer at a dose that duplicates that used in the most recent placebo-controlled clinical trial is safe, improves symptoms, reduces myocardial ischemia and improves EF% at 6 months follow up. Data at 24 months indicate long term preservation of relieved symptoms and reduced ischemic burden, but not of improved EF%. These results must be confirmed by full population analysis and subsequent placebo-controlled trials.
- © 2011 by American Heart Association, Inc.