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Stem cell mobilization by granulocyte-colony-stimulating factor in acute myocardial infarction: lessons from the REVIVAL-2 trial

Abstract

Experimental studies and early-phase clinical trials suggest that mobilization of bone marrow stem cells by granulocyte-colony-stimulating factor (G-CSF) can be used to improve cardiac regeneration after acute myocardial infarction (AMI). In order to more fully evaluate this intervention in patients with AMI, we conducted the Regenerate Vital Myocardium by Vigorous Activation of Bone Marrow Stem Cells (REVIVAL-2) clinical trial. Following successful reperfusion by percutaneous coronary intervention for AMI, patients were randomly assigned to receive a subcutaneous daily dose of 10 µg/kg G-CSF or placebo for 5 days. Treatment with G-CSF produced a significant mobilization of stem cells. After 4–6 months the reduction in infarct size from baseline, as determined by technetium-99-labeled single-photon-emission CT, did not differ significantly between the G-CSF group and the placebo group. Furthermore, the improvement in left ventricular ejection fraction, as assessed by late-enhancement MRI, did not differ significantly between the two groups. G-CSF treatment did not increase the risk of adverse clinical events and did not promote restenosis. Our trial demonstrates that stem cell mobilization by G-CSF does not improve infarct size, left ventricular function, or coronary restenosis in patients with AMI who have had successful mechanical reperfusion.

Key Points

  • G-CSF therapy is safe and feasible in patients with acute myocardial infarction

  • G-CSF treatment does not increase the risk of restenosis

  • No improvement in left ventricular recovery is seen in patients with acute myocardial infarction treated with mechanical reperfusion after G-CSF therapy

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Figure 1: Percentage reduction in infarct size at follow-up in the G-CSF treatment and placebo groups in the REVIVAL-2 trial
Figure 2: Improvement in left ventricular ejection fraction at follow-up in the G-CSF treatment and placebo groups in the REVIVAL-2 trial

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Correspondence to Dietlind Zohlnhöfer.

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Zohlnhöfer, D., Kastrati, A. & Schömig, A. Stem cell mobilization by granulocyte-colony-stimulating factor in acute myocardial infarction: lessons from the REVIVAL-2 trial. Nat Rev Cardiol 4 (Suppl 1), S106–S109 (2007). https://doi.org/10.1038/ncpcardio0745

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