Granulocyte colony-stimulating factor therapy for cardiac repair after acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background: Small clinical studies of granulocyte colony-stimulating factor (G-CSF) therapy for cardiac repair after acute myocardial infarction (MI) have yielded divergent results. The effect of G-CSF therapy on left ventricular (LV) function and structure in these patients remains unclear.

Methods: We searched MEDLINE, EMBASE, Science Citation Index, CINAHL, and the Cochrane CENTRAL database of controlled clinical trials (July 2007) for randomized controlled trials of G-CSF therapy in patients with acute MI. We conducted a fixed-effects meta-analysis across 8 eligible studies (n = 385 patients).

Results: Compared with controls, G-CSF therapy increased LV ejection fraction (EF) by 1.09%, increased LV scar size by 0.22%, decreased LV end-diastolic volume by 4.26 mL, and decreased LV end-systolic volume by 2.50 mL. None of these effects were statistically significant. The risk of death, recurrent MI, and in-stent restenosis was similar in G-CSF-treated patients and controls. Subgroup analysis revealed a modest but statistically significant increase in EF (4.73%, P < .0001) with G-CSF therapy in studies that enrolled patients with mean EF <50% at baseline. Subgroup analysis also showed a significant increase in EF (4.65%, P < .0001) when G-CSF was administered relatively early (< or =37 hours) after the acute event.

Conclusions: Granulocyte colony-stimulating factor therapy in unselected patients with acute MI appears safe but does not provide an overall benefit. Subgroup analyses suggest that G-CSF therapy may be salutary in acute MI patients with LV dysfunction and when started early. Larger randomized studies may be conducted to evaluate the potential benefits of early G-CSF therapy in acute MI patients with LV dysfunction.

Figure 1

Selection of trials for inclusion in meta-analysis. mPBCs, mobilized peripheral blood cells; RCT, randomized controlled trial.

Figure 2

Mean change in LVEF. Forest plot of unadjusted difference in mean (with 95% CIs): G-CSF therapy resulted in a 1.09% (95% CI: -0.21 to 2.38; P=0.10) increase in mean LVEF. The imaging modality is specified within parentheses. FU, follow-up; WMD, weighted mean difference.

Figure 3

Mean change in infarct scar Size. Forest plot of unadjusted difference in mean (with 95% CIs): G-CSF therapy resulted in a 0.22% (95% CI: −1.34 to 1.78; P=0.78) increase in mean infarct scar size. The imaging modality is specified within parentheses. WMD, weighted mean difference.

Figure 4

Mean change in LVEDV. Forest plot of unadjusted difference in mean (with 95% CIs): G-CSF therapy resulted in a 4.26 ml (95% CI: −9.73 to 1.21; P=0.13) reduction in mean LVEDV. The imaging modality is specified within parentheses. FU, follow-up; WMD, weighted mean difference.

Figure 5

Mean change in LVESV. Forest plot of unadjusted difference in mean (with 95% CIs): G-CSF therapy resulted in a 2.50 ml (CI: −7.81 to 2.81; P=0.36) reduction in LVESV. The imaging modality is specified within parentheses. WMD, weighted mean difference.

Figure 6

Mean change in LVEF according to baseline LVEF. Forest plots of unadjusted difference in mean (with 95% CIs) change in LVEF in G-CSF-treated patients compared with controls stratified by the mean LVEF in G-CSF-treated groups at baseline. The interaction between the baseline LVEF and the change in LVEF was also statistically significant (P<0.0001). FU, follow-up; WMD, weighted mean difference.

Figure 7

Mean change in LVEF according to onset of G-CSF therapy. Forest plots of unadjusted difference in mean (with 95% CIs) change in LVEF in G-CSF-treated patients compared with controls stratified by the timing of G-CSF therapy. The interaction between the timing of G-CSF therapy and the change in LVEF was also statistically significant (P<0.0001). FU, follow-up; WMD, weighted mean difference.

Figure 8

Relative risk of adverse clinical outcomes. Forest plot of unadjusted risk ratio (RR, with 95% CIs) for major reported adverse effects, namely, death, recurrent MI, and in-stent restenosis in G-CSF-treated patients compared with controls. None of these end-points were significantly different between groups. FU, follow-up; RR, risk ratio.