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).
Circulation. 2003 Jun 03; 107(21):2677-83.Circ

Abstract

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, 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.

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Authors+Show Affiliations

Hedman M
A.I. Virtanen Institute, University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland.
Hartikainen J
No affiliation info available
Syvänne M
No affiliation info available
Stjernvall J
No affiliation info available
Hedman A
No affiliation info available
Kivelä A
No affiliation info available
Vanninen E
No affiliation info available
Mussalo H
No affiliation info available
Kauppila E
No affiliation info available
Simula S
No affiliation info available
Närvänen O
No affiliation info available
Rantala A
No affiliation info available
Peuhkurinen K
No affiliation info available
Nieminen MS
No affiliation info available
Laakso M
No affiliation info available
Ylä-Herttuala S
No affiliation info available

MeSH

AdenoviridaeAdultAgedAngioplasty, Balloon, CoronaryCardiac CatheterizationChronic DiseaseCoronary RestenosisCoronary VesselsDouble-Blind MethodEndothelial Growth FactorsFeasibility StudiesFemaleFinlandGene Transfer TechniquesGenetic TherapyHumansInjections, Intra-ArterialIntercellular Signaling Peptides and ProteinsLymphokinesMaleMiddle AgedMyocardial IschemiaSafetyStentsTreatment OutcomeVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsVascular Patency

Pub Type(s)

Clinical Trial
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12742981