on May 12, 2003
Published online before print May 12, 2003, doi: 10.1161/01.CIR.0000070540.80780.92
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Submitted on December 31, 2002
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.). * To whom correspondence should be addressed. 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.
Accepted on February 28, 2003
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)
Marja Hedman MD, PhD,
Key words: cardiovascular diseases • gene therapy • angioplasty • stents • perfusion
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Circulation 2003 107: 2635-2637.
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