BACKGROUND:Granulocyte-macrophage colony-stimulating factor (GM-CSF) was recently shown to increase collateral flow index in patients with coronary artery disease. Experimental models showed beneficial effects of GM-CSF on collateral artery growth in the peripheral circulation. Thus, in the present study, we evaluated the effects of GM-CSF in patients with peripheral artery disease. METHODS AND RESULTS: A double-blinded, randomized, placebo-controlled study was performed in 40 patients with moderate or severe intermittent claudication. Patients were treated with placebo or subcutaneously applied GM-CSF (10 microg/kg) for a period of 14 days (total of 7 injections). GM-CSF treatment led to a strong increase in total white blood cell count and C-reactive protein. Monocyte fraction initially increased but thereafter decreased significantly as compared with baseline. Both the placebo group and the treatment group showed a significant increase in walking distance at day 14 (placebo: 127+/-67 versus 184+/-87 meters, P=0.03, GM-CSF: 126+/-66 versus 189+/-141 meters, P=0.04) and at day 90. Change in walking time, the primary end point of the study, was not different between groups. No change in ankle-brachial index was found on GM-CSF treatment at day 14 or at day 90. Laser Doppler flowmetry measurements showed a significant decrease in microcirculatory flow reserve in the control group (P=0.03) and no change in the GM-CSF group. CONCLUSIONS: The present study does not support the use of GM-CSF for treatment of patients with moderate or severe intermittent claudication. Issues that need to be addressed are dosing, the selection of patients, and potential differences between GM-CSF effects in the coronary and the peripheral circulation.
RCT Entities:
BACKGROUND:Granulocyte-macrophage colony-stimulating factor (GM-CSF) was recently shown to increase collateral flow index in patients with coronary artery disease. Experimental models showed beneficial effects of GM-CSF on collateral artery growth in the peripheral circulation. Thus, in the present study, we evaluated the effects of GM-CSF in patients with peripheral artery disease. METHODS AND RESULTS: A double-blinded, randomized, placebo-controlled study was performed in 40 patients with moderate or severe intermittent claudication. Patients were treated with placebo or subcutaneously applied GM-CSF (10 microg/kg) for a period of 14 days (total of 7 injections). GM-CSF treatment led to a strong increase in total white blood cell count and C-reactive protein. Monocyte fraction initially increased but thereafter decreased significantly as compared with baseline. Both the placebo group and the treatment group showed a significant increase in walking distance at day 14 (placebo: 127+/-67 versus 184+/-87 meters, P=0.03, GM-CSF: 126+/-66 versus 189+/-141 meters, P=0.04) and at day 90. Change in walking time, the primary end point of the study, was not different between groups. No change in ankle-brachial index was found on GM-CSF treatment at day 14 or at day 90. Laser Doppler flowmetry measurements showed a significant decrease in microcirculatory flow reserve in the control group (P=0.03) and no change in the GM-CSF group. CONCLUSIONS: The present study does not support the use of GM-CSF for treatment of patients with moderate or severe intermittent claudication. Issues that need to be addressed are dosing, the selection of patients, and potential differences between GM-CSF effects in the coronary and the peripheral circulation.
Authors: Yaohong Tan; Hongwei Shao; Darwin Eton; Zhe Yang; Luis Alonso-Diaz; Hongkun Zhang; Andrew Schulick; Alan S Livingstone; Hong Yu Journal: Cardiovasc Res Date: 2006-12-23 Impact factor: 10.787
Authors: Aoife N Keeling; Timothy J Carroll; Mary M McDermott; Kiang Liu; Yihua Liao; Cormac T Farrelly; William H Pearce; James Carr Journal: Vasc Med Date: 2012-06-27 Impact factor: 3.239
Authors: Mary M McDermott; Luigi Ferrucci; Lu Tian; Jack M Guralnik; Donald Lloyd-Jones; Melina R Kibbe; Tamar S Polonsky; Kathryn Domanchuk; James H Stein; Lihui Zhao; Doris Taylor; Christopher Skelly; William Pearce; Harris Perlman; Walter McCarthy; Lingyu Li; Ying Gao; Robert Sufit; Christina L Bloomfield; Michael H Criqui Journal: JAMA Date: 2017-12-05 Impact factor: 56.272