Abstract 15621: Randomized, Double-Blind, Placebo-Controlled Trial of Autologous CD34+ Cell Therapy for Refractory Angina: 2-Year Safety Analysis
Background: Refractory angina effects 150–250,000 pts in the US alone. These pts have exhausted options for revascularization and continue to have disabling angina despite optimal medical Rx. Pre-clinical studies provided evidence that human CD34+ cells(CD34) can stimulate new blood vessel formation in ischemic myocardium(Myo), improving perfusion and function. We performed a phase II study of intraMyo injection of autologous CD34 in pts with CCS Class 3 and 4 angina to obtain evidence for feasibility, safety and bioactivity.
Methods: A phase II randomized, double-blind, placebo-controlled clinical trial was performed at 26 centers in the US. There were 3 treatment groups: placebo, low dose (1×10^5 CD34/kg body wt) and high dose (5×10^5 CD34/kg). After lot release testing, CD34 were injected endocardially at 10 locations in the ischemic Myo using the Myostar catheter following NOGA mapping. Placebo injections consisted of identical volumes of the diluent only. Pts were followed for 12 mo for efficacy and for an additional 12 mo (24 mo total) for safety outcomes.
Results: A total of 167 pts were randomized and completed the injection procedure and 162, 156 and 130 completed the 6, 12 and 24 mo evals. The low dose treated pts exhibited greater reductions in angina frequency (p=0.02. 0.035) and greater improvements in ETT time (p=0.014, 0.017) than control pts at 6 and 12 mo. The high dose group results were improved over control but not statistically different. An additional year of follow up data was collected for safety endpoints only. At 24 mo there were a total of 7 deaths (12.5%) in the control group (including one during injection procedure) vs 1 (1.8%) in low dose and 2 (3.6%) in high dose (p=0.08). The composite of death, MI, ACS hosp or CHF hosp. occurred at a rate of 33.9%, 21.8% and 16.2%/ 2 yrs in control, low and high dose pts respectively (p=0.08). Full 24 mo safety analysis will be presented.
Conclusions: Autologous CD34 cell therapy was associated with improved exercise tolerance and reduced angina at 1 yr and trends toward reduced MACE at 2 years in no-option pts with intractable angina. These findings provide strong support for proceeding with further clinical development of this therapy to fulfill an unmet medical need in no-option pts with refractory angina.
- © 2010 by American Heart Association, Inc.