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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

A meta-analysis of stem cell mobilization by granulocyte colony-stimulating factor in the treatment of acute myocardial infarction

L Fan, L Chen, X Chen, and F Fu.

Review published: 2008.

Link to full article: [Journal publisher]

CRD summary

This review found no evidence that adding granulocyte colony-stimulating factor (G-CSF) to standard therapy (percutaneous coronary intervention and medication) improved outcomes after a heart attack compared with standard therapy alone. The number of patients in included trials was too small to allow firm conclusions about the safety of G-CSF. The authors’ conclusions and recommendations for research appear reliable.

Authors' objectives

To evaluate the safety and efficacy of granulocyte colony-stimulating factor (G-CSF) added to standard therapy after acute myocardial infarction.


The authors searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials to May 2007 and CINAHL to 2006. Search terms were reported. No language restrictions were imposed. Abstracts from meetings of the American Heart Association, American College of Cardiology and European Society of Cardiology (2002 to 2006) were searched manually and pharmaceutical companies were contacted for details of published and unpublished trials of their G-CSF products.

Study selection

Randomised controlled trials (RCTs) of stem cell mobilization by G-CSF added to standard therapy (percutaneous coronary intervention and conventional medication) versus standard therapy alone were eligible for the review. Eligible participants were patients with a confirmed diagnosis of acute myocardial infarction who underwent percutaneous coronary intervention within 24 hours of onset of symptoms of acute myocardial infarction. G-CSF had to be administered by subcutaneous injection. Primary outcomes were target vessel restenosis (a possible adverse effect of G-CSF) and cumulative cardiac events (a combined endpoint of all-cause mortality, reinfarction and target vessel revascularization), with change in left ventricular ejection fraction from baseline to follow-up as a secondary outcome. Most participants in included studies were male. Mean age varied from 50 to 63 years. G-CSF dose ranged from 2.5 to 10 mg/kg/day. Time from percutaneous coronary intervention to administration of G-CSF ranged from 1.5 to 120 hours.

The authors stated neither how the papers were selected for the review nor how many reviewers performed the selection.

Assessment of study quality

Validity was assessed based on generation of the allocation sequence, allocation concealment, blinding, intention-to-treat analysis and loss to follow up. The authors did not state how the validity assessment was performed.

Data extraction

For dichotomous outcomes, data on numbers of events in each group were extracted and used to calculate the relative risk and associated 95% confidence interval (CI). For left ventricular ejection fraction, the mean and standard deviation of the change from baseline to follow-up were extracted and used to calculate the mean difference and associated 95% CI. If these values were not reported, the mean change in left ventricular ejection fraction in each group was calculated by subtracting the follow-up mean from the baseline mean and the standard deviation calculated using formulae reported in the paper. Two reviewers independently extracted data for the review.

Methods of synthesis

Studies were pooled by meta-analysis using a fixed-effect model; a random-effects model was used if significant heterogeneity was detected. Heterogeneity was assessed by visual inspection of forest plots and using the Χ2 and I2 statistics. When heterogeneity was detected, a sensitivity analysis was performed based on whether a trial was placebo controlled. Publication bias was assessed using a funnel plot and Egger's test.

Results of the review

Six RCTs (n = 320) were included in the review. Mean follow up was 6.17 months (range one to 12 months). Target vessel restenosis and cumulative cardiac events did not differ between groups (pooled relative risk 1.03, 95% CI: 0.68 to 1.55 for restenosis and 0.88, 95% CI: 0.55 to 1.4 for cumulative cardiac events). Heterogeneity was not significant.

Significant heterogeneity was detected for left ventricular ejection fraction and the weighted mean difference suggested no significant difference between groups. A sensitivity analysis involving the five placebo-controlled trials gave a similar result and heterogeneity was no longer significant. The funnel plot and Egger's test did not suggest significant publication bias.

Authors' conclusions

Treatment with G-CSF as an addition to standard therapy for patients with acute myocardial infarction may be safe, but there was limited evidence that treatment improved LVEF compared with standard therapy.

CRD commentary

This review had clear inclusion criteria for participants, intervention, outcomes and study design. The authors searched a range of relevant databases without language restrictions and attempted to locate unpublished studies. Risk of publication bias was assessed. Validity was assessed using appropriate criteria and relevant details of included studies were presented in the text and tables. Data extraction was performed by two independent reviewers, which minimised the risk of errors and bias, but it was unclear whether similar methods were used for study selection and validity assessment. Studies were pooled by meta-analysis. Significant heterogeneity was detected for change in left ventricular ejection fraction, but this was accounted for in a sensitivity analysis. As noted by the authors, the number of trials and patients included in the review was too small to allow firm conclusions about the safety of G-CSF. This was a generally well-conducted review. The authors' cautious conclusions and recommendations for research were in line with the evidence presented and appear reliable.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice.

Research: The authors stated that further RCTs were required to evaluate the efficacy and safety of G-CSF and should focus on the optimal time of administration of G-CSF and its long-term effects.


Natural Science Foundation of Fujian Province, China (no. 2006J0095)

Bibliographic details

Fan L, Chen L, Chen X, Fu F. A meta-analysis of stem cell mobilization by granulocyte colony-stimulating factor in the treatment of acute myocardial infarction. Cardiovascular Drugs and Therapy 2008; 22(1): 45-54. [PubMed: 18000749]

Indexing Status

Subject indexing assigned by NLM


Adult; Aged; Angioplasty, Balloon, Coronary /methods; Combined Modality Therapy; Coronary Restenosis /prevention & control; Female; Granulocyte Colony-Stimulating Factor /adverse effects /therapeutic use; Hematopoietic Stem Cell Mobilization /methods; Humans; Male; Middle Aged; Myocardial Infarction /therapy; Randomized Controlled Trials as Topic; Ventricular Function, Left



Database entry date


Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 18000749

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