TY - JOUR
T1 - Direct intramyocardial plasmid vascular endothelial growth factor-A165 gene therapy in patients with stable severe angina pectoris A randomized double-blind placebo-controlled study
T2 - the Euroinject One trial
AU - Kastrup, Jens
AU - Jørgensen, Erik
AU - Rück, Andreas
AU - Tägil, Kristina
AU - Glogar, Dietmar
AU - Ruzyllo, Witold
AU - Bøtker, Hans Erik
AU - Dudek, Dariusz
AU - Drvota, Viktor
AU - Hesse, Birger
AU - Thuesen, Leif
AU - Blomberg, Pontus
AU - Gyöngyösi, Mariann
AU - Sylvén, Christer
AU - Euroinject One Group
PY - 2005/4/5
Y1 - 2005/4/5
N2 - OBJECTIVES: In the Euroinject One phase II randomized double-blind trial, therapeutic angiogenesis of percutaneous intramyocardial plasmid gene transfer of vascular endothelial growth factor (phVEGF-A(165)) on myocardial perfusion, left ventricular function, and clinical symptoms was assessed.BACKGROUND: Evidence for safety and treatment efficacy have been presented in phase I therapeutic angiogenesis trials.METHODS: Eighty "no-option" patients with severe stable ischemic heart disease, Canadian Cardiovascular Society functional class 3 to 4, were assigned randomly to receive, via the NOGA-MyoStar system (Cordis Corp., Miami Lakes, Florida), either 0.5 mg of phVEGF-A(165) (n = 40) or placebo plasmid (n = 40) in the myocardial region showing stress-induced myocardial perfusion defects on (99m)Tc sestamibi/tetrofosmin single-photon emission computed tomography.RESULTS: No differences among the groups were recorded at baseline with respect to clinical, perfusion, and wall motion characteristics. After three months, myocardial stress perfusion defects did not differ significantly between the VEGF gene transfer and placebo groups (38 +/- 3% and 44 +/- 2%, respectively). Similarly, semiquantitative analysis of the change in perfusion in the treated region of interest did not differ significantly between the two groups. Compared with placebo, VEGF gene transfer improved the local wall motion disturbances, assessed both by NOGA (p = 0.04) and contrast ventriculography (p = 0.03). Canadian Cardiovascular Society functional class classification of angina pectoris improved significantly in both groups but without difference between the groups. No phVEGF-A(165)-related adverse events were observed; however, NOGA procedure-related adverse events occurred in five patients.CONCLUSIONS: The VEGF gene transfer did not significantly improve stress-induced myocardial perfusion abnormalities compared with placebo; however, improved regional wall motion, as assessed both by NOGA and by ventriculography, may indicate a favorable anti-ischemic effect. This result should encourage more studies within the field. Transient VEGF overexpression seems to be safe.
AB - OBJECTIVES: In the Euroinject One phase II randomized double-blind trial, therapeutic angiogenesis of percutaneous intramyocardial plasmid gene transfer of vascular endothelial growth factor (phVEGF-A(165)) on myocardial perfusion, left ventricular function, and clinical symptoms was assessed.BACKGROUND: Evidence for safety and treatment efficacy have been presented in phase I therapeutic angiogenesis trials.METHODS: Eighty "no-option" patients with severe stable ischemic heart disease, Canadian Cardiovascular Society functional class 3 to 4, were assigned randomly to receive, via the NOGA-MyoStar system (Cordis Corp., Miami Lakes, Florida), either 0.5 mg of phVEGF-A(165) (n = 40) or placebo plasmid (n = 40) in the myocardial region showing stress-induced myocardial perfusion defects on (99m)Tc sestamibi/tetrofosmin single-photon emission computed tomography.RESULTS: No differences among the groups were recorded at baseline with respect to clinical, perfusion, and wall motion characteristics. After three months, myocardial stress perfusion defects did not differ significantly between the VEGF gene transfer and placebo groups (38 +/- 3% and 44 +/- 2%, respectively). Similarly, semiquantitative analysis of the change in perfusion in the treated region of interest did not differ significantly between the two groups. Compared with placebo, VEGF gene transfer improved the local wall motion disturbances, assessed both by NOGA (p = 0.04) and contrast ventriculography (p = 0.03). Canadian Cardiovascular Society functional class classification of angina pectoris improved significantly in both groups but without difference between the groups. No phVEGF-A(165)-related adverse events were observed; however, NOGA procedure-related adverse events occurred in five patients.CONCLUSIONS: The VEGF gene transfer did not significantly improve stress-induced myocardial perfusion abnormalities compared with placebo; however, improved regional wall motion, as assessed both by NOGA and by ventriculography, may indicate a favorable anti-ischemic effect. This result should encourage more studies within the field. Transient VEGF overexpression seems to be safe.
KW - Angina Pectoris/diagnostic imaging
KW - Double-Blind Method
KW - Europe
KW - Exercise Test
KW - Female
KW - Genetic Therapy
KW - Humans
KW - Male
KW - Middle Aged
KW - Neovascularization, Pathologic/diagnostic imaging
KW - Plasmids/administration & dosage
KW - Radiopharmaceuticals
KW - Severity of Illness Index
KW - Technetium Tc 99m Sestamibi
KW - Tomography, Emission-Computed, Single-Photon
KW - Treatment Outcome
KW - Vascular Endothelial Growth Factor A/administration & dosage
KW - Ventricular Dysfunction, Left/diagnostic imaging
U2 - 10.1016/j.jacc.2004.12.068
DO - 10.1016/j.jacc.2004.12.068
M3 - Journal article
C2 - 15808751
SN - 0735-1097
VL - 45
SP - 982
EP - 988
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 7
ER -