Autologous CD34+ cell therapy for refractory angina: 2-year outcomes from the ACT34-CMI study

Timothy D. Henry, Gary L. Schaer, Jay H. Traverse, Thomas J. Povsic, Charles Davidson, Joon Sup Lee, Marco A. Costa, Theodore Bass, Farrell Mendelsohn, F. David Fortuin, Carl J. Pepine, Amit N. Patel, Norbert Riedel, Candice Junge, Andrea Hunt, Dean J. Kereiakes, Christopher White, Robert A. Harrington, Richard A. Schatz, Douglas W. Losordo

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

An increasing number of patients have refractory angina despite optimal medical therapy and are without further revascularization options. Preclinical studies indicate that human CD34+ stem cells can stimulate new blood vessel formation in ischemic myocardium, improving perfusion and function. In ACT34-CMI (N = 167), patients treated with autologous CD34+ stem cells had improvements in angina and exercise time at 6 and 12 months compared to placebo; however, the longer-term effects of this treatment are unknown. ACT34 was a phase II randomized, double-blind, placebo-controlled clinical trial comparing placebo, low dose (1 ×105 CD34/ kg body weight), and high dose (5 ×105 CD34/kg) using intramyocardial delivery into the ischemic zone following NOGA® mapping. To obtain longer-term safety and efficacy in these patients, we compiled data of major adverse cardiac events (MACE; death, myocardial infarction, acute coronary syndrome, or heart failure hospitalization) up to 24 months as well as angina and quality of life assessments in patients who consented for 24-month follow-up. A total of 167 patients with class III-IV refractory angina were randomized and completed the injection procedure. The low-dose-treated patients had a significant reduction in angina frequency (p = 0.02, 0.035) and improvements in exercise tolerance testing (ETT) time (p = 0.014, 0.017) compared to the placebo group at 6 and 12 months. At 24 months, patients treated with both low-and high-dose CD34+ cells had significant reduction in angina frequency (p = 0.03). At 24 months, there were a total of seven deaths (12.5%) in the control group versus one (1.8%) in the low-dose and two (3.6%) in the high-dose (p = 0.08) groups. At 2 years, MACE occurred at a rate of 33.9%, 21.8%, and 16.2% in control, low-, and high-dose patients, respectively (p = 0.08). Autologous CD34+ cell therapy was associated with persistent improvement in angina at 2 years and a trend for reduction in mortality in no-option patients with refractory angina.

Original languageEnglish (US)
Pages (from-to)1701-1711
Number of pages11
JournalCell Transplantation
Volume25
Issue number9
DOIs
StatePublished - 2016

Keywords

  • Myocardial ischemia
  • Refractory angina
  • Stem cell therapy

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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    Henry, T. D., Schaer, G. L., Traverse, J. H., Povsic, T. J., Davidson, C., Lee, J. S., Costa, M. A., Bass, T., Mendelsohn, F., Fortuin, F. D., Pepine, C. J., Patel, A. N., Riedel, N., Junge, C., Hunt, A., Kereiakes, D. J., White, C., Harrington, R. A., Schatz, R. A., & Losordo, D. W. (2016). Autologous CD34+ cell therapy for refractory angina: 2-year outcomes from the ACT34-CMI study. Cell Transplantation, 25(9), 1701-1711. https://doi.org/10.3727/096368916X691484