Safety and efficacy of subcutaneous-only granulocyte-macrophage colony-stimulating factor for collateral growth promotion in patients with coronary artery disease

J Am Coll Cardiol. 2005 Nov 1;46(9):1636-42. doi: 10.1016/j.jacc.2005.01.068.


Objectives: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Collateral Circulation / drug effects*
  • Coronary Artery Disease / drug therapy*
  • Double-Blind Method
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage*
  • Granulocyte-Macrophage Colony-Stimulating Factor / adverse effects
  • Humans
  • Injections, Subcutaneous
  • Male
  • Middle Aged


  • Granulocyte-Macrophage Colony-Stimulating Factor