TY - JOUR
T1 - Autologous CD34+ cell therapy for refractory angina
T2 - 2-year outcomes from the ACT34-CMI study
AU - Henry, Timothy D.
AU - Schaer, Gary L.
AU - Traverse, Jay H.
AU - Povsic, Thomas J.
AU - Davidson, Charles
AU - Lee, Joon Sup
AU - Costa, Marco A.
AU - Bass, Theodore
AU - Mendelsohn, Farrell
AU - Fortuin, F. David
AU - Pepine, Carl J.
AU - Patel, Amit N.
AU - Riedel, Norbert
AU - Junge, Candice
AU - Hunt, Andrea
AU - Kereiakes, Dean J.
AU - White, Christopher
AU - Harrington, Robert A.
AU - Schatz, Richard A.
AU - Losordo, Douglas W.
AU - ACT34-CMI Investigators
N1 - Publisher Copyright:
© 2016 Cognizant, LLC.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Myocardial ischemia
KW - Refractory angina
KW - Stem cell therapy
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UR - http://www.scopus.com/inward/citedby.url?scp=84984644943&partnerID=8YFLogxK
U2 - 10.3727/096368916X691484
DO - 10.3727/096368916X691484
M3 - Article
C2 - 27151378
AN - SCOPUS:84984644943
SN - 0963-6897
VL - 25
SP - 1701
EP - 1711
JO - Cell transplantation
JF - Cell transplantation
IS - 9
ER -
