This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (157)  • Contact me when this article is cited  Related Content  • Related letters  • Related articles  • Similar articles in JAMA  Topic Collections  • Cardiovascular System  • Randomized Controlled Trial  • Cardiovascular Disease/ Myocardial Infarction  • Alert me on articles by topic  Social Bookmarking   What's this?

A Randomized Controlled Trial

Dietlind Zohlnhöfer, MD; Ilka Ott, MD; Julinda Mehilli, MD; Kathrin Schömig, MD; Fabian Michalk, MD; Tareq Ibrahim, MD; Günther Meisetschläger, MD; Jasper von Wedel, MD; Hildegard Bollwein, MD; Melchior Seyfarth, MD; Josef Dirschinger, MD; Claus Schmitt, MD; Markus Schwaiger, MD; Adnan Kastrati, MD; Albert Schömig, MD; for the REVIVAL-2 Investigators

JAMA. 2006;295:1003-1010.

Context  Experimental studies and early phase clinical trials suggest that transplantation of blood-derived or bone marrow–derived stem cells may improve cardiac regeneration and neovascularization after acute myocardial infarction. Granulocyte colony-stimulating factor (G-CSF) induces mobilization of bone marrow stem cells.

Objective  To assess the value of stem cell mobilization by G-CSF therapy in patients with acute myocardial infarction.

Design, Setting, and Patients  Randomized, double-blind, placebo-controlled trial of patients diagnosed with ST-segment elevation acute myocardial infarction who had successful reperfusion by percutaneous coronary intervention within 12 hours after onset of symptoms in Germany between February 24, 2004, and February 2, 2005.

Interventions  Patients were randomly assigned to receive subcutaneously either a daily dose of 10 µg/kg of G-CSF or placebo for 5 days.

Main Outcome Measures  The primary end point was reduction of left ventricular infarct size according to technetium Tc 99m sestamibi scintigraphy performed at baseline and at 4 to 6 months after randomization. Secondary end points included improvement of left ventricular ejection fraction measured by magnetic resonance imaging and the incidence of angiographic restenosis.

Results  Of the 114 patients, 56 were assigned to receive treatment with G-CSF and 58 were assigned to receive placebo. Treatment with G-CSF produced a significant mobilization of stem cells. Between baseline and follow-up, left ventricular infarct size according to scintigraphy was reduced by a mean (SD) of 6.2% (9.1%) in the G-CSF group and 4.9% (8.9%) in the placebo group (P = .56) and left ventricular ejection fraction was improved by 0.5% (3.8%) in the G-CSF group and 2.0% (4.9%) in the placebo group (P = .14). Angiographic restenosis occurred in 19 (35.2%) of 54 patients in the G-CSF group and in 17 (30.9%) of 55 patients in the placebo group (P = .79). The most common adverse event among patients assigned to G-CSF was mild to moderate bone pain and muscle discomfort.

Conclusion  Stem cell mobilization by G-CSF therapy in patients with acute myocardial infarction and successful mechanical reperfusion has no influence on infarct size, left ventricular function, or coronary restenosis.

Clinical Trial Registration  ClinicalTrials.gov Identifier: NCT00126100

Author Affiliations: Deutsches Herzzentrum (Drs Zohlnhöfer, Ott, Mehilli, K. Schömig, von Wedel, Schmitt, Kastrati, and A. Schömig), First Medizinische Klinik, Klinikum rechts der Isar (Drs Michalk, Ibrahim, Bollwein, Seyfarth, Dirschinger, and A. Schömig), and Nuklearmedizinische Klinik and Poliklinik rechts der Isar (Drs Meisetschläger and Schwaiger), Technische Universität München, Munich, Germany.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED LETTERS

Granulocyte Colony-Stimulating Factor and Acute Myocardial Infarction
Wolf-Rüdiger Schäbitz, Sigrid Nikol, and Armin Schneider
JAMA. 2006;296(16):1967-1968.
EXTRACT | FULL TEXT  

Granulocyte Colony-Stimulating Factor and Acute Myocardial Infarction
Jaewon Oh, Dae Hyun Kim, and Hyunseok Kang
JAMA. 2006;296(16):1968.
EXTRACT | FULL TEXT  

Granulocyte Colony-Stimulating Factor and Acute Myocardial Infarction—Reply
Dietlind Zohlnhöfer, Ilka Ott, Adnan Kastrati, and Albert Schömig
JAMA. 2006;296(16):1968-1969.
EXTRACT | FULL TEXT  

RELATED ARTICLES

Attempts to Recruit Stem Cells for Repair of Acute Myocardial Infarction: A Dose of Reality
Robert A. Kloner
JAMA. 2006;295(9):1058-1060.
EXTRACT | FULL TEXT  

Granulocyte-Colony Stimulating Factor
Erin Brender, Cassio Lynm, and Richard M. Glass
JAMA. 2006;295(9):1088.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Stem Cell Experiments and Initial Clinical Trial of Cellular Cardiomyoplasty
Guhathakurta et al.
Asian Cardiovasc. Thorac. Ann. 2009;17:581-586.
ABSTRACT | FULL TEXT  

Peripheral blood stem cell mobilisation by granulocyte-colony stimulating factor in patients with acute and old myocardial infarction for intracoronary cell infusion
Chang et al.
Heart 2009;95:1326-1330.
ABSTRACT | FULL TEXT  

Vascular impact of progenitor cell mobilisation for cardiac repair post-myocardial infarction
Freeman and Halcox
Heart 2009;95:1301-1302.
FULL TEXT  

Cell therapies for therapeutic angiogenesis: back to the bench
Sieveking and Ng
Vasc Med 2009;14:153-166.
ABSTRACT  

Granulocyte colony-stimulating factor protects cardiac mitochondria in the early phase of cardiac injury
Hiraumi et al.
Am. J. Physiol. Heart Circ. Physiol. 2009;296:H823-H832.
ABSTRACT | FULL TEXT  

Potential use of endothelial progenitor cells for regeneration of the vasculature
Yamahara and Itoh
Ther Adv Cardiovasc Dis 2009;3:17-27.
ABSTRACT  

Erythropoietin administration after myocardial infarction in mice attenuates ischemic cardiomyopathy associated with enhanced homing of bone marrow-derived progenitor cells via the CXCR-4/SDF-1 axis
Brunner et al.
FASEB J. 2009;23:351-361.
ABSTRACT | FULL TEXT  

Insights into mechanisms behind arteriogenesis: what does the future hold?
van Oostrom et al.
J. Leukoc. Biol. 2008;84:1379-1391.
ABSTRACT | FULL TEXT  

Clinical view on experimental stem cell and cytokine research in cardiac disease
Kische et al.
Eur Heart J Suppl 2008;10:K2-K6.
ABSTRACT | FULL TEXT  

Granulocyte colony-stimulating factor exacerbates cardiac fibrosis after myocardial infarction in a rat model of permanent occlusion
Cheng et al.
Cardiovasc Res 2008;80:425-434.
ABSTRACT | FULL TEXT  

Stem cell mobilization utilizing granulocyte colony stimulating factor in advanced chronic heart failure: lessons from a pilot study
Joseph et al.
Eur Heart J Suppl 2008;10:K24-K26.
ABSTRACT | FULL TEXT  

Safety and efficacy of intracoronary infusion of mobilized peripheral blood stem cell in patients with myocardial infarction: MAGIC Cell-1 and MAGIC Cell-3-DES-trials
Kang and Kim
Eur Heart J Suppl 2008;10:K39-K43.
ABSTRACT | FULL TEXT  

Autologous bone marrow stem cell mobilization induced by granulocyte colony-stimulating factor after myocardial infarction
Valgimigli et al.
Eur Heart J Suppl 2008;10:K27-K34.
ABSTRACT | FULL TEXT  

Intracoronary infusion of autologous mononuclear cells from bone marrow or granulocyte colony-stimulating factor-mobilized apheresis product may not improve remodelling, contractile function, perfusion, or infarct size in a swine model of large myocardial infarction
de Silva et al.
Eur Heart J 2008;29:1772-1782.
ABSTRACT | FULL TEXT  

Review: Endothelial progenitor cells: markers of vascular reparative capacity
Povsic and Goldschmidt-Clermont
Ther Adv Cardiovasc Dis 2008;2:199-213.
ABSTRACT  

Cardiovascular events and re-stenosis following administration of G-CSF in acute myocardial infarction: systematic review and meta-analysis
Ince et al.
Heart 2008;94:610-616.
ABSTRACT | FULL TEXT  

Thymosin {beta}4 Is an Essential Paracrine Factor of Embryonic Endothelial Progenitor Cell-Mediated Cardioprotection
Hinkel et al.
Circulation 2008;117:2232-2240.
ABSTRACT | FULL TEXT  

Stem Cell Mobilization by Granulocyte Colony-Stimulating Factor for Myocardial Recovery After Acute Myocardial Infarction: A Meta-Analysis
Zohlnhofer et al.
J Am Coll Cardiol 2008;51:1429-1437.
ABSTRACT | FULL TEXT  

Parathyroid hormone treatment after myocardial infarction promotes cardiac repair by enhanced neovascularization and cell survival
Zaruba et al.
Cardiovasc Res 2008;77:722-731.
ABSTRACT | FULL TEXT  

Biologic and molecular effects of granulocyte colony-stimulating factor in healthy individuals: recent findings and current challenges
Anderlini and Champlin
Blood 2008;111:1767-1772.
ABSTRACT | FULL TEXT  

Primary hyperparathyroidism is associated with increased circulating bone marrow-derived progenitor cells
Brunner et al.
Am. J. Physiol. Endocrinol. Metab. 2007;293:E1670-E1675.
ABSTRACT | FULL TEXT  

Bone Marrow Derived Mesenchymal Cell Mobilization by Granulocyte-Colony Stimulating Factor After Acute Myocardial Infarction: Results From the Stem Cells in Myocardial Infarction (STEMMI) Trial
Ripa et al.
Circulation 2007;116:I-24-I-30.
ABSTRACT | FULL TEXT  

Bone Marrow-Derived CXCR4+ Cells Mobilized by Macrophage Colony-Stimulating Factor Participate in the Reduction of Infarct Area and Improvement of Cardiac Remodeling after Myocardial Infarction in Mice
Morimoto et al.
Am. J. Pathol. 2007;171:755-766.
ABSTRACT | FULL TEXT  

Potential risks of bone marrow cell transplantation into infarcted hearts
Breitbach et al.
Blood 2007;110:1362-1369.
ABSTRACT | FULL TEXT  

The Year in Interventional Cardiology
Dixon et al.
J Am Coll Cardiol 2007;50:270-285.
FULL TEXT  

Evolution of Left Ventricular Ejection Fraction and its Relationship to Infarct Size After Acute Myocardial Infarction
Ndrepepa et al.
J Am Coll Cardiol 2007;50:149-156.
ABSTRACT | FULL TEXT  

Granulocyte Colony-Stimulating Factor and Granulocyte Macrophage Colony-Stimulating Factor Exacerbate Atherosclerosis in Apolipoprotein E-Deficient Mice
Haghighat et al.
Circulation 2007;115:2049-2054.
ABSTRACT | FULL TEXT  

Clinical trials with adult stem/progenitor cells for tissue repair: let's not overlook some essential precautions
Prockop and Olson
Blood 2007;109:3147-3151.
FULL TEXT  

Mobilization of CD34-Positive Bone Marrow-Derived Cells After Coronary Stent Implantation: Impact on Restenosis
Inoue et al.
Circulation 2007;115:553-561.
ABSTRACT | FULL TEXT  

Importance of collateral circulation in coronary heart disease
Berry et al.
Eur Heart J 2007;28:278-291.
ABSTRACT | FULL TEXT  

M-CSF Accelerates Neointimal Formation in the Early Phase After Vascular Injury in Mice: The Critical Role of the SDF-1-CXCR4 System
Shiba et al.
Arterioscler. Thromb. Vasc. Bio. 2007;27:283-289.
ABSTRACT | FULL TEXT  

The Year in Cardiac Imaging
Gibbons et al.
J Am Coll Cardiol 2006;48:2324-2339.
FULL TEXT  

Myocardial regeneration induced by granulocyte-colony-stimulating factor mobilization of stem cells in patients with acute or chronic ischaemic heart disease: a non-invasive alternative for clinical stem cell therapy?
Kastrup et al.
Eur Heart J 2006;27:2748-2754.
ABSTRACT | FULL TEXT  

G-CSF in the setting of acute myocardial infarction
Ince et al.
Eur Heart J Suppl 2006;8:H40-H45.
ABSTRACT | FULL TEXT  

Granulocyte-Colony-Stimulating Factor Mobilizes Bone Marrow Stem Cells in Patients With Subacute Ischemic Stroke: The Stem Cell Trial of Recovery EnhanceMent After Stroke (STEMS) Pilot Randomized, Controlled Trial (ISRCTN 16784092)
Sprigg et al.
Stroke 2006;37:2979-2983.
ABSTRACT | FULL TEXT  

Angiogenic cells can be rapidly mobilized and efficiently harvested from the blood following treatment with AMD3100
Shepherd et al.
Blood 2006;108:3662-3667.
ABSTRACT | FULL TEXT  

Imaging Stem Cells Implanted in Infarcted Myocardium
Zhou et al.
J Am Coll Cardiol 2006;48:2094-2106.
ABSTRACT | FULL TEXT  

Granulocyte colony-stimulating factor and acute myocardial infarction.
Schabitz et al.
JAMA 2006;296:1967-1968.
FULL TEXT  

Granulocyte colony-stimulating factor and acute myocardial infarction.
Oh et al.
JAMA 2006;296:1968-1968.
FULL TEXT  

Autologous Bone Marrow Stem Cell Mobilization Induced by Granulocyte Colony-Stimulating Factor After Subacute ST-Segment Elevation Myocardial Infarction Undergoing Late Revascularization: Final Results From the G-CSF-STEMI (Granulocyte Colony-Stimulating Factor ST-Segment Elevation Myocardial Infarction) Trial
Engelmann et al.
J Am Coll Cardiol 2006;48:1712-1721.
ABSTRACT | FULL TEXT  

Potential Hazards and Technical Considerations Associated With Myocardial Cell Transplantation Protocols for Ischemic Myocardial Syndrome
Ben-Dor et al.
J Am Coll Cardiol 2006;48:1519-1526.
ABSTRACT | FULL TEXT  

Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium
Kolossov et al.
JEM 2006;203:2315-2327.
ABSTRACT | FULL TEXT  

Effects of Granulocyte Colony Stimulating Factor on Functional Activities of Endothelial Progenitor Cells in Patients With Chronic Ischemic Heart Disease
Honold et al.
Arterioscler. Thromb. Vasc. Bio. 2006;26:2238-2243.
ABSTRACT | FULL TEXT  

Aging Impairs the Beneficial Effect of Granulocyte Colony-Stimulating Factor and Stem Cell Factor on Post-Myocardial Infarction Remodeling
Lehrke et al.
Circ. Res. 2006;99:553-560.
ABSTRACT | FULL TEXT  

Post-infarct heart repair with granulocyte-colony stimulating factor: Is it a utopian goal?
Pagliaro
Cardiovasc Res 2006;71:405-407.
FULL TEXT  

Cardiac Stem Cell Therapy: Need for Optimization of Efficacy and Safety Monitoring
Oettgen
Circulation 2006;114:353-358.
FULL TEXT  

Developing Granulocyte-Colony Stimulating Factor for the Treatment of Stroke: Current Status of Clinical Trials
Schabitz and Schneider
Stroke 2006;37:1654-1654.
FULL TEXT  

Fourth Annual American College of Cardiology International Lecture: A Journey in the Interventional Field
Serruys
J Am Coll Cardiol 2006;47:1754-1768.
FULL TEXT  

Leaking Capillaries and White Lung in Sepsis--Is Angiopoietin 2 the Culprit?: Excess Circulating Angiopoietin-2 May Contribute to Pulmonary Vascular Leak in Sepsis in Humans. PLoS Medicine 3: e46, 2006
S.M. et al.
J. Am. Soc. Nephrol. 2006;17:1207-1217.
FULL TEXT  

Synergism of Hematopoietic Cytokines for Infarct Repair
Cho and Yoon
Circ. Res. 2006;98:990-992.
FULL TEXT  

The End of Granulocyte Colony-Stimulating Factor in Acute Myocardial Infarction?: Reaping the Benefits Beyond Cytokine Mobilization
Hill and Bartunek
Circulation 2006;113:1926-1928.
FULL TEXT  

Failure of One Type of Stem-Cell Therapy for Acute MI
JWatch General 2006;2006:2-2.
FULL TEXT  

Attempts to Recruit Stem Cells for Repair of Acute Myocardial Infarction: A Dose of Reality
Kloner
JAMA 2006;295:1058-1060.
FULL TEXT