Granulocyte colony-stimulating factor therapy for stem cell mobilization following anterior wall myocardial infarction: the CAPITAL STEM MI randomized trial.

Abstract

BACKGROUND:

Small studies have yielded divergent results for administration of granulocyte colony-stimulating factor (G-CSF) after acute myocardial infarction. Adequately powered studies involving patients with at least moderate left ventricular dysfunction are lacking.

METHODS:

Patients with left ventricular ejection fraction less than 45% after anterior-wall myocardial infarction were treated with G-CSF (10 μg/kg daily for 4 days) or placebo. After initial randomization of 86 patients, 41 in the placebo group and 39 in the G-CSF group completed 6-month follow-up and underwent measurement of left ventricular ejection fraction by radionuclide angiography.

RESULTS:

Baseline and 6-week mean ejection fraction was similar for the G-CSF and placebo groups: 34.8% (95% confidence interval [CI] 32.6%-37.0%) v. 36.4% (95% CI 33.5%-39.2%) at baseline and 39.8% (95% CI 36.2%-43.4%) v. 43.1% (95% CI 39.2%-47.0%) at 6 weeks. However, G-CSF therapy was associated with a lower ejection fraction at 6 months relative to placebo (40.8% [95% CI 37.4%-44.2%] v. 46.0% [95% CI 42.7%-44.3%]). Both groups had improved left ventricular function, but change in left ventricular ejection fraction was lower in patients treated with G-CSF than in those who received placebo (5.7 [95% CI 3.4-8.1] percentage points v. 9.2 [95% CI 6.3-12.1] percentage points). One or more of a composite of several major adverse cardiac events occurred in 8 patients (19%) within each group, with similar rates of target-vessel revascularization.

INTERPRETATION:

In patients with moderate left ventricular dysfunction following anterior-wall infarction, G-CSF therapy was associated with a lower 6-month left ventricular ejection fraction but no increased risk of major adverse cardiac events. Future studies of G-CSF in patients with left ventricular dysfunction should be monitored closely for safety.

TRIAL REGISTRATION:

ClinicalTrials.gov, no. NCT00394498.

• Authors: Benjamin Hibbert, Bradley Hayley, Robert S Beanlands, Michel Le May, Richard Davies, Derek So, Jean-François Marquis, Marino Labinaz, Michael Froeschl, Edward R O'Brien, Ian G Burwash, George A Wells, Ali Pourdjabbar, Trevor Simard, Harold Atkins, Christopher Glover
• Journal: CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne (CMAJ) Vol. 186 Issue 11 Pg. E427-34 (Aug 05 2014) ISSN: 1488-2329 [Electronic] Canada
• PMID: 24934893 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Canadian Medical Association or its licensors.

Chemical References

• Granulocyte Colony-Stimulating Factor

Topics

• Anterior Wall Myocardial Infarction (etiology, physiopathology, therapy)
• Double-Blind Method
• Female
• Follow-Up Studies
• Granulocyte Colony-Stimulating Factor (therapeutic use)
• Hematopoietic Stem Cell Mobilization (methods)
• Humans
• Male
• Middle Aged
• Prospective Studies
• Radionuclide Imaging
• Stroke Volume
• Treatment Outcome
• Ventricular Dysfunction, Left (complications, diagnostic imaging, physiopathology, therapy)
• Ventricular Remodeling