Promotion of Collateral Growth by Granulocyte-Macrophage Colony-Stimulating Factor in Patients With Coronary Artery Disease: A Randomized, Double-Blind, Placebo-Controlled Study

Abstract

Background Experimentally, activated macrophages have been documented to induce vascular proliferation. Methods and Results In 21 patients (age 74±9 years) with extensive coronary artery disease not eligible for coronary artery bypass surgery, the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF, Molgramostim) on quantitatively assessed collateral flow was tested in a randomized, double-blind, placebo-controlled fashion. The study protocol consisted of an invasive collateral flow index (CFI) measurement immediately before intracoronary injection of 40 μg of GM-CSF (n=10) or placebo (n=11) and after a 2-week period with subcutaneous GM-CSF (10 μg/kg) or placebo, respectively. CFI was determined by simultaneous measurement of mean aortic pressure (P ao , mm Hg), distal coronary occlusive pressure (P occl , mm Hg; using intracoronary sensor guidewires), and central venous pressure (CVP, mm Hg): CFI=(P occl −CVP)/(P ao −CVP). CFI, expressing collateral flow during coronary occlusion relative to normal antegrade flow during vessel patency, changed from 0.21±0.14 to 0.31±0.23 in the GM-CSF group ( P <0.05) and from 0.30±0.16 to 0.23±0.11 in the placebo group ( P =NS). The treatment-induced difference in CFI was +0.11±0.12 in the GM-CSF group and -0.07±0.12 in the placebo group ( P =0.01). ECG signs of myocardial ischemia during coronary balloon occlusion occurred in 9 of 10 patients before and 5 of 10 patients after GM-CSF treatment ( P =0.04), whereas they were observed in 5 of 11 patients before and 8 of 11 patients after placebo ( P =NS). Conclusions This first clinical study investigating the potential of GM-CSF to improve collateral flow in patients with coronary artery disease documents its efficacy in a short-term administration protocol.