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).
Hedman, Marja MD, PhD*; Hartikainen, Juha MD, PhD*; Syvanne, Mikko MD, PhD, FESC; Stjernvall, Joachim MD, PhD; Hedman, Antti MD, PhD; Kivela, Antti MD; Vanninen, Esko MD, PhD; Mussalo, Hanna MD; Kauppila, Esa MD; Simula, Sakari MD, PhD; Narvanen, Outi PhD; Rantala, Arto MD; Peuhkurinen, Keijo MD, PhD, FESC; Nieminen, Markku S. MD, PhD, FESC; Laakso, Markku MD, PhD; Yla-Herttuala, Seppo MD, PhD, FESC
107(21):2677-2683, June 3, 2003.
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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 [mu]g of DNA with 2000 [mu]L 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.
(C) 2003 American Heart Association, Inc.