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.


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, 2x10(10) pfu), 28 patients received VEGF plasmid liposome (VEGF-P/L; 2000 microg of DNA with 2000 microL 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.
Hedman
Marja
M
A.I. Virtanen Institute, University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland.
Hartikainen
Juha
J
Syvänne
Mikko
M
Stjernvall
Joachim
J
Hedman
Antti
A
Kivelä
Antti
A
Vanninen
Esko
E
Mussalo
Hanna
H
Kauppila
Esa
E
Simula
Sakari
S
Närvänen
Outi
O
Rantala
Arto
A
Peuhkurinen
Keijo
K
Nieminen
Markku S
MS
Laakso
Markku
M
Ylä-Herttuala
Seppo
S
D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D006328:Cardiac Catheterization; D002908:Chronic Disease; D023903:Coronary Restenosis / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004311:Double-Blind Method; D016228:Endothelial Growth Factors / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D005240:Feasibility Studies; D005260:Female; D005387:Finland; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007269:Injections, Intra-Arterial; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D008222:Lymphokines / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000628:therapy*; D012449:Safety; D015607:Stents / Q000009:adverse effects*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014654:Vascular Patency / Q000187:drug effects
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors