Granulocyte colony stimulating factor treatment following a heart attack

People who suffer a heart attack (due to a blockage in the artery supplying blood to the heart) are usually affected by the damage to a portion of their heart muscle. Current treatment options are unable to restore the damaged section of the heart. Recently, stem cells have been shown to be able to restore and replace the damaged tissue in patients with heart attack. These cells could be mobilized to the heart with agents such as granulocyte colony stimulating factor (G-CSF).

In this review, analysis of seven included studies with low risk of bias using G-CSF to improve the function of damaged heart of patient with heart attack failed to show any beneficial effects of this treatment. The rate of mortality was not different between the two groups (RR 0.64, 95% CI 0.15 to 2.80, P = 0.55). Also, left ventricular parameters including left ventricular ejection fraction (RR 3.41, 95% CI -0.61 to 7.44, P = 0.1), end systolic volume (RR -1.35, 95% CI -4.68 to 1.99, P = 0.43) and end diastolic volume (RR -4.08, 95% CI -8.28 to 0.12, P = 0.06) did not show significant changes between the treatment and the control groups. There was no evidence that the study was associated with serious adverse effects, however it should be noted that the study was limited since the trials included lacked long enough follow up durations. Additionally four studies had either high or unclear risk of bias for blinding. Therefore, based on the results of the current study, G-CSF treatment should not be administered for patients with heart attack.

Authors' conclusions: 

Limited evidence from small trials suggested a lack of benefit of G-CSF therapy in patients with AMI. Since data of the risk of bias regarding blinding of personnel were not conclusive, larger RCTs with appropriate power calculations and longer follow up durations are required in order to address current uncertainties regarding the clinical efficacy and therapy-related adverse events of G-CSF treatment.

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Background: 

Acute myocardial infarction (AMI) is the leading cause of death in developed countries, and current treatment modalities have failed to regenerate the dead myocardium resulting from the ischemic damage. Stem cells have the potential to regenerate the damaged myocardium. These cells can be mobilized from the bone marrow by factors such as granulocyte colony stimulating factor (G-CSF).

Objectives: 

To assess the effects of stem cell mobilization following granulocyte colony stimulating factor therapy in patients with acute myocardial infarction.

Search strategy: 

We searched CENTRAL (The Cochrane Library Issue 4, 2010), MEDLINE (1950 to November week 3, 2010), EMBASE (1980 to 2010 week 48), BIOSIS Previews (1969 to 30 November 2010), ISI Science Citation Index Expanded (1970 to 4 December 2010) and ISI Conference Proceedings Citation Index - Science (1990 to 4 December 2010). We also checked reference lists of articles.

Selection criteria: 

We included randomized controlled trials including participants with a clinical diagnosis of AMI who were randomly allocated to the subcutaneous administration of G-CSF through a daily dose of 2.5, 5 or 10 microgram/kg for four to six days or placebo. No age or other restrictions were applied for the selection of patients.

Data collection and analysis: 

Two authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data regarding the clinical efficacy and adverse outcomes. Disagreements were resolved by the third author.

Main results: 

We included seven trials reported in 30 references in the review (354 participants). In all trials, G-CSF was compared with placebo preparations. Dosage of G-CSF varied among studies, ranging from 2.5 to 10 microgram/kg/day. Regarding overall risk of bias, data regarding the generation of randomization sequence and incomplete outcome data were at a low risk of bias; however, data regarding binding of personnel were not conclusive. The rate of mortality was not different between the two groups (RR 0.64, 95% CI 0.15 to 2.80, P = 0.55). Regarding safety, the limited amount of evidence is inadequate to reach any conclusions regarding the safety of G-CSF therapy. Moreover, the results did not show any beneficial effects of G-CSF in patients with AMI regarding left ventricular function parameters, including left ventricular ejection fraction (RR 3.41, 95% CI -0.61 to 7.44, P = 0.1), end systolic volume (RR -1.35, 95% CI -4.68 to 1.99, P = 0.43) and end diastolic volume (RR -4.08, 95% CI -8.28 to 0.12, P = 0.06). It should also be noted that the study was limited since the trials included lacked long enough follow up durations.

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