Published online before print May 12, 2003, doi: 10.1161/01.CIR.0000070540.80780.92
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(Circulation. 2003;107:2677.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Safety and Feasibility of Catheter-Based Local Intracoronary Vascular Endothelial Growth Factor Gene Transfer in the Prevention of Postangioplasty and In-Stent Restenosis and in the Treatment of Chronic Myocardial Ischemia
Phase II Results of the Kuopio Angiogenesis Trial (KAT)
From A.I. Virtanen Institute, University of Kuopio (M.H., O.N., S.Y.-H.); the Department of Medicine, Kuopio University Hospital (M.H., J.H., A.H., A.K., S.S., A.R., K.P., M.L., S.Y.-H.), and the Department of Cardiology, University of Helsinki and Helsinki University Central Hospital (M.S., J.S., M.S.N.); the Department of Clinical Physiology and Nuclear Medicine (E.V., H.M., E.K., S.S.,) and the Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland (S.Y.-H.).
Correspondence to Dr Seppo Ylä-Herttuala, A.I. Virtanen Institute, University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland. E-mail Seppo.YlaHerttuala{at}uku.fi
Background— Catheter-based intracoronary vascular endothelial growth factor (VEGF) gene transfer is a potential treatment for coronary heart disease. However, only limited data are available about local VEGF gene transfer given during angioplasty (PTCA) and stenting.
Methods and Results— Patients with coronary heart disease (n=103; Canadian Cardiovascular Society class II to III; mean age, 58±6 years) were recruited in this randomized, placebo-controlled, double-blind phase II study. PTCA was performed with standard methods, followed by gene transfer with a perfusion-infusion catheter. Ninety percent of the patients were given stents; 37 patients received VEGF adenovirus (VEGF-Adv, 2x1010 pfu), 28 patients received VEGF plasmid liposome (VEGF-P/L; 2000 µg of DNA with 2000 µL of DOTMA:DOPE [1:1 wt/wt]), and 38 control patients received Ringer’s lactate. Follow-up time was 6 months. Gene transfer to coronary arteries was feasible and well tolerated. The overall clinical restenosis rate was 6%. In quantitative coronary angiography analysis, the minimal lumen diameter and percent of diameter stenosis did not significantly differ between the study groups. However, myocardial perfusion showed a significant improvement in the VEGF-Adv-treated patients after the 6-month follow-up. Some inflammatory responses were transiently present in the VEGF-Adv group, but no increases were detected in the incidences of serious adverse events in any of the study groups.
Conclusions— Gene transfer with VEGF-Adv or VEGF-P/L during PTCA and stenting shows that (1) intracoronary gene transfer can be performed safely (no major gene transfer-related adverse effects were detected), (2) no differences in clinical restenosis rate or minimal lumen diameter were present after the 6-month follow-up, and (3) a significant increase was detected in myocardial perfusion in the VEGF-Adv-treated patients.
Key Words: cardiovascular diseases • gene therapy • angioplasty • stents • perfusion
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