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Kuopio Angiogenesis Trial - KAT II
Description:
The goal of the Kuopio Angiogenesis Trial (KAT II) was to compare the efficacy of local vascular endothelial growth factor (VEGF) gene transfer versus placebo given during percutaneous transluminal coronary angioplasty (PTCA) and stenting.
Hypothesis:
To determine the safety and feasibility of VEGF adenovirus (VEGF-Adv) and VEGF plasmid liposome (VEGF-P/L) gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of myocardial ischemia.
Study Design
Study Design:
Patients Enrolled: 103
Mean Follow Up: Six-month angiographic; safety follow-up mean 28 months
Mean Patient Age: Mean age 58 years
Female: 23
Patient Populations:
Age 38 to 75 years, stable CCS class II to III angina, 60-99% diameter stenosis in one to two of the main coronary arteries in coronary angiography suitable for catheter-based revascularization, diameter of the target vessel 2.5-4.0 mm, no prior PTCA of the target vessel, and no contraindications for aspirin or heparin
Exclusions:
Diffuse coronary disease, ostial lesions, complex anatomy of the coronary arteries, lesions at bifurcations, length of stenosis >20 mm, acute myocardial infarction, unstable angina, acute upper respiratory tract infection, diabetes, or malignancy
Primary Endpoints:
MLD and percent diameter stenosis at six-month angiographic follow-up
Secondary Endpoints:
Myocardial perfusion, exercise tolerance, incidence of new cardiac events, emergency or elective angiography or revascularization, functional class, working ability, and need for peroral nitrates at six-month follow-up
Drug/Procedures Used:
Patients were randomized to VEGF-Adv (n=37), VEGF-P/L (n=28), or placebo (using Ringer’s lactate; n=38). Arterial gene transfer was performed at the site of PTCA immediately after the angioplasty but before stent implantation, using an infusion-perfusion catheter.
Concomitant Medications:
All patients received aspirin and heparin. Patients receiving stents were also prescribed ticlodipine or clopidogrel.
Principal Findings:
Ninety percent of patients received a stent in addition to PTCA. Neither minimal lumen diameter (MLD) nor percent stenosis differed at six-month angiographic follow-up for the three arms (MLD 1.98 mm vs. 2.15 mm vs. 2.08 mm, p=NS; stenosis 34% vs. 29% vs. 26% for VEGF-Adv vs. VEGF-P/L vs. control arms, respectively, p=NS).
Clinical restenosis of Canadian Cardiovascular Society (CCS) class II to III angina occurred in three patients in both VEGF-Adv and control arms, and no patients in the VEGF-P/L arm (p=NS). Myocardial perfusion improved significantly from baseline in the VEGF-Adv group after the six-month follow-up, but did not differ from baseline in the VEGF-P/L arm or control arm.
In the VEGF-Adv arm, there was one death, which was due to a ruptured aortic aneurysm 20 months after the gene transfer, and one patient with sarcoidosal granulomas in the eye and parotid gland. In the VEGF-P/L arm, there were two new cancers (malignant glioma and hypernephroma). Fever (>37.5°C) occurred most frequently in the VEGF-Adv arm (51% for VEGF-Adv vs. 39% VEGF-P/L vs. 3% control; p<0.005 Adv vs. control, p<0.05 for P/L vs. control).
Interpretation:
Among patients with coronary heart disease undergoing PTCA and stenting, treatment with local VEGF gene transfer via adenovirus or plasmid liposome was not associated with a difference in six-month MLD or percent stenosis compared with placebo. While there was no apparent efficacy benefit with the VEGF therapy, there did not appear to be serious safety concerns during the mean 28-month follow-up. Despite the lack of efficacy in the primary endpoint, the secondary endpoint of myocardial perfusion was significantly improved in the VEGF-Adv arm compared with baseline.
References:
Hedman M, Hartikainen J, Syvanne M, et al. 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;107:2677-2683.
Keywords: Glioma, Follow-Up Studies, Heparin, Constriction, Pathologic, Granuloma, Neoplasm Recurrence, Local, Angioplasty, Balloon, Coronary, Stents, Parotid Gland, Liposomes, Coronary Angiography, Vascular Endothelial Growth Factor A, Carcinoma, Renal Cell, Plasmids, Coronary Vessels
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