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

Selection of trials for inclusion in meta-analysis. mPBCs, Mobilized peripheral blood cells.

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 = .10) increase in mean LVEF. The imaging modality is specified within parentheses. FU, Follow-up; WMD, weighted mean difference.

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 = .78) increase in mean infarct scar size. The imaging modality is specified within parentheses.

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 = .13) reduction in mean LVEDV. The imaging modality is specified within parentheses.

Mean change in LVESV. Forest plot of unadjusted difference in mean (with 95% CIs): G-CSF therapy resulted in a 2.50-mL (95% CI: −7.81 to 2.81, P = .36) reduction in LVESV. The imaging modality is specified within parentheses.

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 < .0001).

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 < .0001).

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.

Forest plot of unadjusted difference in mean (with 95% CIs) change in LVEF in G-CSF-treated patients compared with controls in RCTs that used a uniform G-CSF dose of 10 μg/kg/day. The figure shows the summary of the included RCTs. G-CSF therapy resulted in a 0.72% (95% CI: −2.25 to 0.81; P = .19) decrease in mean LVEF. The imaging modality is specified within parentheses. FU, follow-up; G-CSF, granulocyte colony-stimulating factor; LVEF, left ventricular ejection fraction; WMD, weighted mean difference.

Forest plot of unadjusted difference in mean (with 95% CIs) change in infarct scar size in G-CSF-treated patients compared with controls in RCTs that used a uniform G-CSF dose of 10 μg/kg/day. The figure shows the summary of the included RCTs. G-CSF therapy resulted in a 0.28% (95% CI: −2.22 to 1.65; P = .77) increase in mean infarct scar size. The imaging modality is specified within parentheses. G-CSF, granulocyte colony-stimulating factor; WMD, weighted mean difference.

Forest plot of unadjusted difference in mean (with 95% CIs) change in LVEDV in G-CSF-treated patients compared with controls in RCTs that used a uniform G-CSF dose of 10 μg/kg/day. The figure shows the summary of the included RCTs. G-CSF therapy resulted in a 2.94 mL (95% CI: −11.03 to 5.14; P = .48) increase in mean LVEDV. The imaging modality is specified within parentheses. FU, follow-up; G-CSF, granulocyte colony-stimulating factor; LVEDV, left ventricular end-diastolic volume; WMD, weighted mean difference.

Forest plot of unadjusted difference in mean (with 95% CIs) change in LVESV in G-CSF-treated patients compared with controls in RCTs that used a uniform G-CSF dose of 10 μg/kg/day. The figure shows the summary of included RCTs. G-CSF therapy resulted in a 1.27 mL (CI: −7.04 to 4.50; P = .67) increase in LVESV. The imaging modality is specified within parentheses. G-CSF, granulocyte colony-stimulating factor; LVESV, left ventricular end-systolic volume; WMD, weighted mean difference.

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 in RCTs that used a uniform G-CSF dose of 10 μg/kg/day. The figure shows the summary of included RCTs. The RR of death was 1.32 (CI: 0.27 to 6.48), RR of recurrent MI was 0.97 (CI: 0.14 to 6.48), and RR of in-stent restenosis was 0.97 (CI: 0.63 to 1.51). None of these end-points were significantly different between groups. FU, follow-up; G-CSF, granulocyte colony-stimulating factor; MI, myocardial infarction; RR, risk ratio.

Forest plot of unadjusted difference in mean (with 95% CIs) change in LVEF in G-CSF-treated patients compared with controls. All eligible RCTs that included patients with acute MI as well as chronic ischemic cardiomyopathy were included. The figure shows the summary of the included RCTs. G-CSF therapy resulted in a 1.62% (95% CI: −1.76 to 5.00; P = .35) increase in mean LVEF. The imaging modality is specified within parentheses. FU, follow-up; G-CSF, granulocyte colony-stimulating factor; LVEF, left ventricular ejection fraction; WMD, weighted mean difference.

Forest plot of unadjusted difference in mean (with 95% CIs) change in infarct scar size in G-CSF-treated patients compared with controls. All eligible RCTs that included patients with acute MI as well as chronic ischemic cardiomyopathy were included. The figure shows the summary of the included RCTs. The imaging modality is specified within parentheses. G-CSF therapy resulted in a 0.25% (95% CI: −1.27 to 1.77; P = .75) increase in mean infarct scar size. G-CSF, granulocyte colony-stimulating factor; WMD, weighted mean difference.

Forest plot of unadjusted difference in mean (with 95% CIs) change in LVEDV in G-CSF-treated patients compared with controls. All eligible RCTs that included patients with acute MI as well as chronic ischemic cardiomyopathy were included. The figure shows the summary of the included RCTs. G-CSF therapy resulted in a 3.22 mL (95% CI: −10.97 to 4.53; P = .42) decrease in mean LVEDV. The imaging modality is specified within parentheses. FU, follow-up; G-CSF, granulocyte colony-stimulating factor; LVEDV, left ventricular end-diastolic volume; WMD, weighted mean difference.

Forest plot of unadjusted difference in mean (with 95% CIs) change in LVESV in G-CSF-treated patients compared with controls. All eligible RCTs that included patients with acute MI as well as chronic ischemic cardiomyopathy were included. The figure shows the summary of included RCTs. G-CSF therapy resulted in a 3.07 mL (CI: −11.08 to 4.94; P = .45) decrease in LVESV. The imaging modality is specified within parentheses. G-CSF, granulocyte colony-stimulating factor; LVESV, left ventricular end-systolic volume; WMD, weighted mean difference.

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. All eligible RCTs that included patients with acute MI as well as chronic ischemic cardiomyopathy were included. The figure shows the summary of included RCTs. The RR of death was 1.08 (CI: 0.27 to 4.40), RR of recurrent MI was 1.54 (CI: 0.32 to 7.37), and RR of in-stent restenosis was 1.02 (CI: 0.70 to 1.47). None of these end-points were significantly different between groups. FU, follow-up; G-CSF, granulocyte colony-stimulating factor; MI, myocardial infarction; RR, risk ratio.

Funnel plot of the included studies showing the publication bias and the consistency of the study results around the mean outcome. The Funnel plots were done for each of the outcomes separately (panels A-E). Where inconsistency was high, the funnel plots were not interpretable; where inconsistency was low, the funnel plots were inconclusive. LV, left ventricular; LVEDV, LV end-diastolic volume; LVEF, LV ejection fraction; LVESV, LV end-systolic volume.

Funnel plot of the included studies showing the publication bias and the consistency of the study results around the mean outcome. The Funnel plots were done for each of the outcomes separately (panels A-E). Where inconsistency was high, the funnel plots were not interpretable; where inconsistency was low, the funnel plots were inconclusive. LV, left ventricular; LVEDV, LV end-diastolic volume; LVEF, LV ejection fraction; LVESV, LV end-systolic volume.