G-CSF Shows Positive Safety, Efficacy Signals After STEMI in Preliminary Studies
NEW YORK, NY—Results from a pair of small, randomized studies suggest that using granulocyte-colony stimulating factor (G-CSF) to mobilize stem cells is safe and may improve long-term cardiac function in patients with acute myocardial infarction. Researchers discussed variations of the strategy, for use in the setting of primary percutaneous coronary intervention (PCI), January 23, 2013, at the Eighth International Conference on Cell Therapy for Cardiovascular Disease.
Better Function, Few Events
Giulio Pompilio, MD, PhD, of the University of Milan (Milan, Italy), presented 3-year data from the prospective, multicenter STEM-AMI trial, which enrolled 56 patients with anterior STEMI who had LVEF below 45% after reperfusion at 5 Italian sites between January 2006 and December 2009. Patients were randomized to PCI and standard care plus a 10 µg/Kg dose of G-CSF (n = 27) or placebo (n = 29).
Clinical follow-up at 34 months was available in 51 patients (91.1%). Event rates were low and similar between cohorts at all time points. Two patients in the study arm and 1 in the control arm died at 3 years, while 4 patients treated with G-CSF and 1 in the control group were hospitalized for heart failure. One patient in each group had a stroke.
At 3 years, only placebo-treated patients experienced an absolute decrease in ejection fraction vs. baseline (-6.5%; P < 0.01), while the study arm only showed a trend in the same direction (-2.5%; P = NS).
End-systolic volume grew 33.1 mL in the placebo group and 17.3 mL in the G-CSF group. From 180 days to 3 years, the increases in volume were 25.6 mL and 17.1 mL, respectively.
End-diastolic volume increased 47.8 mL in the placebo group and 24.1 mL in the G-CSF group between baseline and 3 years. From 180 days to 3 years, it rose 28.2 mL and 23.3 mL in the placebo and G-CSF groups, respectively. By 3 years, end-diastolic volume was lower with G-CSF than with placebo at 168.4 mL vs. 194.9 mL (P < 0.04).
“There should be no safety concerns for G-CSF administration in anterior STEMI in the long-term,” Dr. Pompilio said. “The observed pattern of LV dilation suggests that the active effect of G-CSF treatment occurs mostly in the healing phase of infarction, within 6 months.”
Moreover, the 3-year absolute reduction in end-diastolic volume in the active treatment group was independent from the infarct-related baseline variables of NT-pro-BNP, Killip score, troponin I, and time-to-reperfusion, he observed. “Our data suggest an association between circulating levels of CD34+ after mobilization and long-term LV functional parameters,” Dr. Pompilio concluded.
Testing Combination Therapy
A second presentation focused on whether the antihyperglycemic drug sitagliptin, typically used to treat type 2 diabetes, might augment G-CSF treatment. Wolfgang-Michael Franz, MD, PhD, of the Ludwig Maximilians University (Munich, Germany), shared early data from the SITAGRAMI study, which finished enrolling patients in July 2012.
For SITAGRAMI, 174 AMI patients within 24 hours of symptom onset were randomized to treatment with 10 µg G-CSF per day for 5 days plus 100 µg sitagliptin for 28 days (n = 87) or NaCl 0.9% for 5 days plus placebo for 28 days (n = 87).
Interim 6-week data show that in 36 patients receiving dual G-CSF and sitagliptin therapy there has been only 1 instance each of de novo stenosis and in-stent restenosis. Per these results so far, “dual stem cell therapy seems to be safe in the early phase,” Dr. Franz said.
Ongoing follow-up will assess the primary endpoint of change in global cardiac ejection fraction from baseline to 6 months, restenosis at 6 months, and MACE at 12 months.
Sources:1. Pompilio G. STEM-AMI trial: cMRI and other observations at 3 years. Presented at: Eighth International Conference on Cell Therapy for Cardiovascular Disease; January 23, 2013; New York, NY.
2. Franz W-M. Sitagliptin plus granulocyte-colony stimulating factor in acute myocardial infarction. Presented at: Eighth International Conference on Cell Therapy for Cardiovascular Disease; January 23, 2013; New York, NY.
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Disclosures
- Dr. Giulio reports receiving grant support and consulting fees from the Pail Corporation and serving as an advisory board member for Cytori Therapeutics.
- Dr. Franz reports receiving research support from Heinz-Nixdorf-Stiftung.
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