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 v ascular endothelial growth factor (rhVEGF) has resulted in successful revas cularization of ischemic myocardium. This was a dose escalation trial desig ned to determine the safety and tolerability of intracoronary rhVEGF infusi ons. Methods and Results Patients were eligible if they had stable exertional an gina, a significant reversible perfusion defect by stress myocardial perfus ion study, and coronary anatomy that was suboptimal for percutaneous corona ry intervention or coronary artery bypass grafting. rhVEGF was administered to a total of 15 patients by 2 sequential (eg, right and left) intracorona ry infusions, each for 10 minutes, at rates of 0.005 (n = 4), 0.017 (n = 4) , 0.050 (n = 4), and 0.167 mug/kg/min (n = 3). Pharmacokinetic sampling and hemodynamic monitoring were performed for 24 hours. Radionuclide myocardia l perfusion imaging was performed before treatment and at 30 and 60 days af ter treatment. Follow-up angiograms were performed on selected patients at 60 days. The maximally tolerated intracardiac dose of rhVEGF was 0.050 mug/ kg/min. Minimal hemodynamic changes were seen at 0.0050 mug/kg/min (2% +/- 7% [SD] mean decrease in systolic blood pressure from baseline to nadir sys tolic blood pressure), whereas at 0.167 mug/kg/min there was a 28% +/- 7% m ean 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 patien ts with follow-up angiograms had improvements in the collateral density sco re. Conclusion rhVEGF appears well tolerated by coronary infusion at rates up t o 0.050 mug/kg/min. This study provides the basis for future clinical trial s to assess the clinical benefit of therapeutic angiogenesis with rhVEGF.