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Angiogenic gene therapy in patients with nonrevascularizable ischemic heart disease: a phase 2 randomized, controlled trial of AdVEGF121 (AdVEGF121) versus maximum medical treatment
- Source :
- Gene Therapy. 13:1503-1511
- Publication Year :
- 2006
- Publisher :
- Springer Science and Business Media LLC, 2006.
-
Abstract
- The demonstration that angiogenic growth factors can stimulate new blood vessel growth and restore perfusion in animal models of myocardial ischemia has led to the development of strategies designed for the local production of angiogenic growth factors in patients who are not candidates for conventional revascularization. The results of recent clinical trials of proangiogenesis gene therapy have been disappointing; however, significant limitations in experimental design, in particular in gene transfer strategies, preclude drawing definitive conclusions. In the REVASC study cardiac gene transfer was optimized by direct intramyocardial delivery of a replication-deficient adenovirus-containing vascular endothelial growth factor (AdVEGF121, 4 x 10(10) particle units (p.u.)). Sixty-seven patients with severe angina due to coronary artery disease and no conventional options for revascularization were randomized to AdVEGF121 gene transfer via mini-thoracotomy or continuation of maximal medical treatment. Exercise time to 1 mm ST-segment depression, the predefined primary end-point analysis, was significantly increased in the AdVEGF121 group compared to control at 26 weeks (P=0.026), but not at 12 weeks. As well, total exercise duration and time to moderate angina at weeks 12 and 26, and in angina symptoms as measured by the Canadian Cardiovascular Society Angina Class and Seattle Angina Questionnaire were all improved by VEGF gene transfer (all P-values at 12 and 26 weeks < or =0.001). However, if anything the results of nuclear perfusion imaging favored the control group, although the AdVEGF121 group achieved higher workloads. Overall there was no significant difference in adverse events between the two groups, despite the fact that procedure-related events were seen only in the thoracotomy group. Therefore, administration of AdVEGF121 by direct intramyocardial injections resulted in objective improvement in exercise-induced ischemia in patients with refractory ischemic heart disease.
- Subjects :
- Male
Vascular Endothelial Growth Factor A
medicine.medical_specialty
medicine.medical_treatment
Genetic Vectors
Myocardial Ischemia
Ischemia
Neovascularization, Physiologic
Perfusion scanning
Revascularization
Injections, Intramuscular
Adenoviridae
law.invention
Angina
Coronary artery disease
Electrocardiography
Randomized controlled trial
Transduction, Genetic
law
Internal medicine
Genetics
medicine
Humans
Molecular Biology
Antihypertensive Agents
Tomography, Emission-Computed, Single-Photon
Analysis of Variance
business.industry
Vascular disease
Heart
Genetic Therapy
Canadian Cardiovascular Society
Middle Aged
medicine.disease
Surgery
Treatment Outcome
Exercise Test
Cardiology
Molecular Medicine
Drug Therapy, Combination
Female
Safety
business
Subjects
Details
- ISSN :
- 14765462 and 09697128
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Gene Therapy
- Accession number :
- edsair.doi.dedup.....8ae0ab8438538d8193785c25e40a105a