Abstract 16278: 10-Year Follow up Assessment of a Phase I Trial of Angiogenic Gene Therapy for the Treatment of Coronary Artery Disease Using Direct Intramyocardial Administration Vascular Endothelial Growth Factor 121
Background: Based on studies in experimental animals demonstrating that AdVEGF121, an E1-E3- serotype 5 adenovirus coding for the 121 isoform of vascular endothelial growth factor, could mandate the generation of new blood vessels and reverse coronary ischemia, clinical studies of direct myocardial administration of AdVEGF121 were initiated in patients with late stage coronary artery disease. This study provides long-term follow-up on these patients having undergone adenoviral-based administration of angiogenic mediators to the myocardium.
Methods: From 1997 to 1999, AdVEGF was administered by direct myocardial injection to an area of reversible ischemia in 31 patients with severe coronary disease, either as an adjunct to conventional coronary artery bypass grafting (Group A, n = 15) or as sole therapy using a mini-thoracotomy (Group B, n = 16). Ten year follow-up was obtained for these patients.
Results: Follow-up was complete in 29 (94%) of patients. The five year survival in Group A was 10/15 (67%) and 11/16 (69%) in Group B. Ten year survival was 6/15 (40%) and 5/16 (31%) for these patients, respectively. Mortality was associated with greater age and a higher incidence of diabetes and hypertension at the time of initial surgery. During the time of follow-up (median 11.8 years), four patients developed potentially treatment-related complications, including one patient with retinopathy and three patients (10%) with malignancies (one each with prostate cancer, colon cancer, and lymphoma/squamous cell cancer of the head), consistent with an expected 14% incidence of malignancy predicted in this age population. Several patients also underwent subsequent cardiac-related procedures, including repeat vascularization (n=5), ICD placement (n=6), and one cardiac transplantation. At ten year follow- up, five of the six living Group A patients and three of the four living Group B patients (excluding the transplant) had a CCS Angina Class of 1 or 2.
Conclusion: This small case series of high-risk patients that received myocardial administration of AdVEGF documents that AdVEGF may be safely administered with minimal long term related morbidity and mortality. Future larger trials appear warranted to confirm these preliminary findings.
- © 2011 by American Heart Association, Inc.