Eight-year safety follow-up of coronary artery disease patients after local intracoronary VEGF gene transfer

Vascular endothelial growth factor (VEGF) has been shown to stimulate angiogenesis and myocardial perfusion. The short-term safety of VEGF gene therapy is excellent. However, there are only limited results regarding the long-term effects. The Kuopio Angiogenesis Trial (KAT) studied the efficiency and short-term safety of the local VEGF-A(165) gene transfer in 103 patients with coronary artery disease. Three patient groups received either VEGF as an adenoviral (n = 37), or as a plasmid/liposome vector (n = 28), or as a placebo (n = 38), during coronary angioplasty and stenting (percutaneous coronary intervention, PCI)AQ1. The aim of this study was to examine the long-term effects and safety of VEGF gene therapy. Patients were interviewed by telephone or with a questionnaire on their current status of health, coronary and other cardiovascular events and symptoms, working ability, exercise tolerance, other diseases, such as cancer and diabetes, as well as their personal experience of the treatment. Causes of death were clarified from hospital records. The total follow-up time was 8.1 years (range 6.9-9.7 years). Overall 82% of the patients were reached across the study. Eight (7.5%) of the patients died during the follow-up, but there was no significant difference in mortality between the groups (3/32 vs 2/26 vs 3/31 VEGF-adenovirus vs VEGF-plasmid/liposome vs placebo, respectively; P = 0.88). The incidence of major adverse cardiovascular events (MACEs) (10 vs 11 vs 15; P = 0.85), cancer (1 vs 4 vs 2; P = 0.38) or diabetes (2 vs 2 vs 2; P = 0.97) did not differ between the groups. Local intracoronary VEGF gene transfer is safe and does not increase the risk of MACE, arrhythmias, cancer, diabetes or other diseases. Gene Therapy (2009) 16, 629-634; doi: 10.1038/gt.2009.4; published online 12 February 2009