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Granulocyte colony stimulating factor in chronic angina to stimulate neovascularisation: a placebo controlled crossover trial
  1. Sharon Chih1,2,
  2. Peter S Macdonald1,2,3,
  3. Jane A McCrohon2,3,
  4. David Ma2,3,
  5. John Moore2,3,
  6. Michael P Feneley1,2,3,
  7. Matthew Law3,
  8. Jason C Kovacic4,
  9. Robert M Graham1,2,3
  1. 1Victor Chang Cardiac Research Institute, Sydney, Australia
  2. 2St Vincent's Hospital, Sydney, Australia
  3. 3University of New South Wales, Sydney, Australia
  4. 4Cardiovascular Institute, Mount Sinai Hospital, New York, New York, USA
  1. Correspondence to Professor R M Graham, Victor Chang Cardiac Research Institute, Lowy Packer Building, 405 Liverpool St, Darlinghurst, NSW 2010, Australia; b.graham{at}


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.

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  • Funding This study was supported by RT Hall Estate, MBF, St Vincent's Clinic Foundation and Pfizer Cardiovascular Lipid Grant.

  • Competing interests None.

  • Ethics approval Ethics approval was provided by St Vincent's Hospital Human Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.