title: Autologous CD34+Cell Therapy for Refractory Angina: 2-Year Outcomes From the ACT34-CMI Study.
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 × 105CD34/kg body weight), and high dose (5 × 105CD34/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.
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Henry
authors.forename: Gary L
authors.initials: GL
authors.lastname: Schaer
authors.forename: Jay H
authors.initials: JH
authors.lastname: Traverse
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Povsic
authors.forename: Charles
authors.initials: C
authors.lastname: Davidson
authors.forename: Joon Sup
authors.initials: JS
authors.lastname: Lee
authors.forename: Marco A
authors.initials: MA
authors.lastname: Costa
authors.forename: Theodore
authors.initials: T
authors.lastname: Bass
authors.forename: Farrell
authors.initials: F
authors.lastname: Mendelsohn
authors.forename: F David
authors.initials: FD
authors.lastname: Fortuin
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Pepine
authors.forename: Amit N
authors.initials: AN
authors.lastname: Patel
authors.forename: Norbert
authors.initials: N
authors.lastname: Riedel
authors.forename: Candice
authors.initials: C
authors.lastname: Junge
authors.forename: Andrea
authors.initials: A
authors.lastname: Hunt
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Kereiakes
authors.forename: Christopher
authors.initials: C
authors.lastname: White
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Richard A
authors.initials: RA
authors.lastname: Schatz
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Losordo
mesh_terms: D000787:Angina Pectoris / Q000628:therapy*; D018952:Antigens, CD34 / Q000378:metabolism*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D004311:Double-Blind Method; D005080:Exercise Test; D006801:Humans; D009206:Myocardium / Q000473:pathology; D013234:Stem Cells / Q000378:metabolism* / Q000502:physiology; D014182:Transplantation, Autologous / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34