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)

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, 2 x 10(10) pfu), 28 patients received VEGF plasmid liposome (VEGF-P/L; 2000 mug of DNA with 2000 muL 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.