Clinical outcome after stem cell mobilization with granulocyte-colony-stimulating factor after acute ST-elevation myocardial infarction: 5-year results of the STEMMI trial

Abstract

Background. Granulocyte-colony-stimulating factor (G-CSF) has been investigated in trials aiming to promote recovery of myocardial function after myocardial infarction. Long-term safety-data have never been reported. A few studies indicated an increased risk of in-stent re-stenosis. We aimed to investigate clinical events 5 years after inclusion into a randomized trial of G-CSF versus placebo. Methods. Seventy-eight patients were randomized, from 2003–2005, to G-CSF or placebo after myocardial infarction. Four patients withdrew consent prior to study treatment and were excluded leaving 36 and 38 in the placebo- and G-CSF groups. Information about all hospital admittances of included patients until 2010 was extracted from a national register. The only censoring event was immigration. The events were combined into four prespecified endpoints: Time to (1) first hospital admittance (all cause), (2) first cardiovascular-related hospital admittance, (3) first major cardiovascular event, and (4) death. Results. One patient (1%) was lost to follow-up. Four patients (4%) died in the follow-up period, three in the G-CSF group and one in the placebo group (p = 0.4). Hazard ratio for all cause hospital admittance was 0.7 (95% CI 0.38–1.29). The incidence of both new myocardial infarction (p = 1.0) and revascularization procedures (p = 0.4) were similar in the two groups. Survival analyses showed no differences in the occurrence of any of the four prespecified composite endpoints between the two groups (p = 0.6; 0.5; 0.8; 0.3). Conclusions. We found no indication of increased risk of adverse events up to 5 years after G-CSF treatment. These results support the continued investigation of G-CSF for cardiac therapy.

Key Words::

• Myocardial infarction
• G-CSF
• follow-up studies
• randomized controlled trial
• stem cells

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

The STEMMI trial was supported by grants from The Danish Heart Foundation (grant number 0442B18-A1322141), Copenhagen, Denmark; Danish Stem Cell Research Doctoral School, Odense, Denmark; The Faculty of Health Sciences, Copenhagen University, Denmark; The Research Foundation of Rigshospitalet, Copenhagen, Denmark; Raimond og Dagmar Ringgård-Bohn's Foundation, Copenhagen, Denmark; Aase og Ejnar Danielsens Foundation, Lyngby, Denmark; Erik og Martha Scheibels Foundation, Odense, Denmark; and Arvid Nilssons Foundation, Hvidovre, Denmark.