G-CSF Fails to Improve Long-Term Clinical Outcomes in REVIVAL-2 Trial


Granulocyte-Colony Stimulating Factor (G-CSF) is a glycoprotein (protein with sugars attached to it) that signals to the bone marrow to produce granulated white blood cells (specifically neutrophils), and to release stem cells and progenitor cells into the peripheral circulation.

This function of G-CSF makes it a candidate treatment for patients who have recently experienced a heart attack, since the release of stem cells from the bone marrow could, in theory, bring more stem cells to the damaged heart to heal it. Additionally, G-CSF is known to induce the proliferation and enhance the survival of heart muscle cells.

In several experiments with laboratory animals showed that G-CSF treatments after a heart attack significantly reduced mortality (Moazzami K, Roohi A, and Moazzimi B. Cochrane Database Systematic Reviews 2013; 5: CD008844. However, in a clinical trial known as the REVIVAL-2 trial, a double-blind, placebo-controlled study, G-CSG treatment failed to influence the performance of the heart six months after administration.

Now Birgit Steppich and others have published a seven-year follow-up of the subjects in the original REVIVAL-2 study to determine if G-CSF had long-term benefits that were not revealed in the short-term study. These results were published in the journal Thrombosis and Haemostasis (115.4/2016).

Of the initially enrolled 114 patients, 106 patients completed the seven-year follow-up. The results of this trial showed that G-CSF treatment for five days in successfully revascularized heart attack patients did not alter the incidence of death, recurrent heart attacks, stroke, or secondary adverse heart events during the seven-year follow-up.

These results are similar to those of the STEMMI trial, which treated patients with G-CSF for six days 10-65 hours after the reperfusion. In a five-year follow-up of 74 patients, there were no differences in the occurrence of major cardiovascular events between the G-CSF-treated group and the placebo group (Achili F, et al., Heart 2014; 100: 574-581).

Therefore, it appears that even though G-CSF worked in laboratory rodents that had suffered heart attacks, this treatment does not consistently benefit human heart attack patients. Although why it does not work will almost certainly require more insights than we presently possess.

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Published by

mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).