Granulocyte colony stimulating factor in chronic angina to stimulate neovascularisation: a placebo controlled crossover trial

Sharon Chih, Peter S Macdonald, Jane A McCrohon, David Ma, John Moore, Michael P Feneley, Matthew Law, Jason C Kovacic, Robert M Graham
Heart 2012, 98 (4): 282-90

BACKGROUND: Experimental studies demonstrate that granulocyte colony stimulating factor (G-CSF) promotes neovascularisation and confers cardioprotection.

OBJECTIVE: To assess the efficacy of repeated low dose G-CSF plus exercise on myocardial ischaemia in patients with severe chronic ischaemic heart disease.

METHODS: 18 patients with Canadian Cardiovascular Society class III-IV angina completed a randomised, double blind, crossover study of dose adjusted G-CSF versus placebo. Exercise was commenced 6 weeks prior and continued for the duration of the study. G-CSF or placebo was administered daily for 5 consecutive days at fortnightly intervals for three cycles, followed by crossover after 6 weeks. Primary outcome was myocardial perfusion by cardiac magnetic resonance imaging (MRI). Secondary outcomes were: Seattle Angina and Utility Based Quality of Life Heart Questionnaire (SAQ/UBQ-H), Exercise Stress Test (EST) and quantification of endothelial progenitor cells (EPC) by flow cytometry and angiogenic cytokines by immunoassay.

RESULTS: Compared with placebo, G-CSF had no effect on myocardial ischaemia by cardiac MRI, EST or SAQ/UBQ-H, despite effective EPC mobilisation (peak fold increase: CD34+ =19, CD34+ CD133+ = 37, CD34+ vascular endothelial growth factor receptor 2 (VEGFR-2)+ = 5, CD34+ CD133+ VEGFR-2+ = 3; all p<0.05 vs. placebo). Plasma levels of stromal cell derived factor 1, angiopoietin 1, interleukin 8 and tumour necrosis factor α decreased after a symptom limited EST while vascular endothelial growth factor and platelet derived growth factor remained unchanged. All cytokines were unchanged following G-CSF. Seven troponin I positive events occurred with G-CSF compared with three with placebo (p=0.289). High sensitivity C reactive protein and N terminal prohormone brain natriuretic peptide increased with G-CSF (both p<0.01 vs. placebo).

CONCLUSION: In patients with chronic ischaemic heart disease, G-CSF mobilises EPCs but does not improve myocardial perfusion or angina. G-CSF increases plasma levels of adverse prognostic cardiac biomarkers. Clinical trial registration information Australian New Zealand Clinical Trials Registry: Unique identifier: ACTRN012607000354482.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"