Intracoronary administration of recombinant human vascular endothelial growth factor to patients with coronary artery disease.
BACKGROUND
Patients with severe myocardial ischemia who are not candidates for percutaneous or surgical revascularization have few therapeutic options. Therapeutic angiogenesis in animal models with use of recombinant human vascular endothelial growth factor (rhVEGF) has resulted in successful revascularization of ischemic myocardium. This was a dose escalation trial designed to determine the safety and tolerability of intracoronary rhVEGF infusions.


RESULTS
Patients were eligible if they had stable exertional angina, a significant reversible perfusion defect by stress myocardial perfusion study, and coronary anatomy that was suboptimal for percutaneous coronary intervention or coronary artery bypass grafting. rhVEGF was administered to a total of 15 patients by 2 sequential (eg, right and left) intracoronary infusions, each for 10 minutes, at rates of 0.005 (n = 4), 0.017 (n = 4), 0.050 (n = 4), and 0.167 mg/kg/min (n = 3). Pharmacokinetic sampling and hemodynamic monitoring were performed for 24 hours. Radionuclide myocardial perfusion imaging was performed before treatment and at 30 and 60 days after treatment. Follow-up angiograms were performed on selected patients at 60 days. The maximally tolerated intracardiac dose of rhVEGF was 0.050 mg/kg/min. Minimal hemodynamic changes were seen at 0.0050 mg/kg/min (2% +/- 7% [SD] mean decrease in systolic blood pressure from baseline to nadir systolic blood pressure), whereas at 0.167 mg/kg/min there was a 28% +/- 7% mean decrease from baseline to nadir (136 to 95 mm Hg systolic). Myocardial perfusion imaging was improved in 7 of 14 patients at 60 days. All 7 patients with follow-up angiograms had improvements in the collateral density score.


CONCLUSIONS
rhVEGF appears well tolerated by coronary infusion at rates up to 0.050 mg/kg/min. This study provides the basis for future clinical trials to assess the clinical benefit of therapeutic angiogenesis with rhVEGF.
Henry
T D
TD
Divisions of Cardiology, Hennepin County Medical Center, Minneapolis, MN, USA. henry003@maroon.tc.umn.edu
Rocha-Singh
K
K
Isner
J M
JM
Kereiakes
D J
DJ
Giordano
F J
FJ
Simons
M
M
Losordo
D W
DW
Hendel
R C
RC
Bonow
R O
RO
Eppler
S M
SM
Zioncheck
T F
TF
Holmgren
E B
EB
McCluskey
E R
ER
D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy*; D016228:Endothelial Growth Factors / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008222:Lymphokines / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D018919:Neovascularization, Physiologic / Q000187:drug effects; D020033:Protein Isoforms / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D020033:Protein Isoforms; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors