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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.

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