Abstract 11855: High Doses of Vegf165 as Sole Gene Therapy for Patients with Inoperable Coronary Artery Disease and Refractory Angina: 1-Year Follow-Up From a Phase I/ii Clinical Trial
Background: Gene therapy using specific cytokines has potential to induce angiogenesis and improve collateral circulation in ischemic tissue. There is debate of what are the most appropriate gene, vector, dose and route of delivery.
Hypothesis: High doses of VEGF165 as sole gene therapy for patients with refractory angina is safe and can improve myocardial perfusion of ischemic areas.
Methods: Phase I/II clinical trial. Thirteen patients with refractory angina, coronary anatomy unfeasible for coronary bypass or angioplasty and myocardial ischemic area of at least 5% assessed by single positron emission tomography (SPECT) were included. Before inclusion, they were maintained for at least 6 months under optimized treatment and as symptoms and ischemic area persisted, they received transthoracic intramyocardial injections of 2000 µg VEGF165 plasmidial. Evaluation included SPECT, treadmill tests using Naughton protocol, Minnesotta Quality of Life Questionnaire (QOL) and New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) angina classifications.
Results: During the first phase of clinical treatment, there was worsening of rest ischemia scores (P<0.05). Three months after VEGF165 therapy, SPECT scores showed a reduction in number of ischemic segments under stress (pre-op 18.38±7.51 vs. 15.31±7.30; P<0.01) and at rest (pre-op 13.23±7.98 vs.8.77±6.82; P<0.01). Six months after intervention, there was a significant difference only in rest ischemia score (6 months: 16.92±7.27; P<0.01). One year after gene therapy the ischemia scores were similar to the preoperative values, although there were improvements of number of performed stages (pre-op 2.46±2.07 vs.12 months 4.15±2.23; P<0.01) and oxygen consumption (pre-op 7.66±4.47 vs.12 months 10.89±4.65; P<0.05) in treadmill test, QOL (pre-op 48.23±18.35 vs.12 months 28.31±18.14; P<0.01) scores and CCS (pre-op 3(3-3.5) vs.12 months 2(1-2.5); P<0.01) and NYHA (pre-op 3(3-3) vs. 2(2-2) vs. 12 months 2(1-2); P<0.01) classification.
Conclusions: Gene therapy demonstrated to be feasible and safe. There was significant improvement in clinical parameters of angina and transitory, but well defined, increase in myocardial perfusion of the treated ischemic areas.
- © 2011 by American Heart Association, Inc.