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

Chih, Sharon and Macdonald, Peter S and McCrohon, Jane A and Ma, David and Moore, John and Feneley, Michael P and Law, Matthew and Kovacic, Jason C and Graham, Robert M (2012) Granulocyte colony stimulating factor in chronic angina to stimulate neovascularisation: a placebo controlled crossover trial. Heart (British Cardiac Society), 98 (4). pp.282-90. ISSN 1468-201X (PP OA)

[thumbnail of Chih 2012 GCSF trial _Heart PP.pdf]
Preview
Text
Chih 2012 GCSF trial _Heart PP.pdf

Download (707kB) | Preview

Abstract

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: http://www.anzctr.org.au. Unique identifier: ACTRN012607000354482.
(RT Hall Estate, MBF, St Vincent’s Clinic Foundation and Pfizer Cardiovascular Lipid Grants).

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 21 Dec 2015 22:48
Last Modified: 22 May 2018 04:41
URI: https://eprints.victorchang.edu.au/id/eprint/41

Actions (login required)

View Item View Item