title: Safety and efficacy of subcutaneous-only granulocyte-macrophage colony-stimulating factor for collateral growth promotion in patients with coronary artery disease.
abstract: OBJECTIVE
  This study was designed to investigate the safety and efficacy of a short-term subcutaneous-only granulocyte-macrophage colony-stimulating factor (GM-CSF) protocol for coronary collateral growth promotion.
  
  
  BACKGROUND
  The safety and efficacy of an exclusively systemic application of GM-CSF in patients with coronary artery disease (CAD) and collateral artery promotion has not been studied so far.
  
  
  METHODS
  In 14 men (age 61 +/- 11 years) with chronic stable CAD, the effect of 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 in a stenotic as well as a normal coronary artery before and after a two-week period with subcutaneous GM-CSF (10 microg/kg; n = 7) or placebo (n = 7). Collateral flow index was determined by simultaneous measurement of mean aortic, distal coronary occlusive, and central venous pressure.
  
  
  RESULTS
  Collateral flow index in all vessels changed from 0.116 +/- 0.05 to 0.159 +/- 0.07 in the GM-CSF group (p = 0.028) and from 0.166 +/- 0.06 to 0.166 +/- 0.04 in the placebo group (p = NS). The treatment-induced difference in CFI was +0.042 +/- 0.05 in the GM-CSF group and -0.001 +/- 0.04 in the placebo group (p = 0.035). Among 11 determined cytokines, chemokines, and their monocytic receptor concentrations, the treatment-induced change in CFI was predicted by the respective change in tumor necrosis factor-alpha concentration. Two of seven patients in the GM-CSF group and none in the placebo group suffered an acute coronary syndrome during the treatment period.
  
  
  CONCLUSIONS
  A subcutaneous-only, short-term protocol of GM-CSF is effective in promoting coronary collateral artery growth among patients with CAD. However, the drug's safety regarding the occurrence of acute coronary syndrome is questionable.
authors.affiliation: Department of Cardiology, University Hospital, Bern, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Zbinden
authors.forename: Rainer
authors.initials: R
authors.lastname: Zbinden
authors.forename: Pascal
authors.initials: P
authors.lastname: Meier
authors.forename: Stephan
authors.initials: S
authors.lastname: Windecker
authors.forename: Christian
authors.initials: C
authors.lastname: Seiler
mesh_terms: D000368:Aged; D003097:Collateral Circulation / Q000187:drug effects*; D003324:Coronary Artery Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor