Abstract 17214: Autologous CD34+ Cell Therapy Reduces Mortality and Improves Exercise Capacity in Patients With Refractory Angina
Introduction: Phase I, II and prematurely terminated phase III trials of autologous CD34+ cell therapy provide consistent evidence for improving exercise time, angina and trends towards reductions in mortality, but these studies were not individually powered for efficacy.
Hypothesis: Combined analysis of studies enrolling comparable patients with refractory angina and assessing similar endpoints will define the efficacy and safety of autologous CD34+ stem cell therapy for treatment of this debilitating condition.
Methods: Mean and standard deviation exercise times were estimated across the treatment arms by calculating an average for each, weighting by the sample sizes. Meta-analytic methods were applied to calculate the best estimate of treatment effect in exercise time across the standardized differences and to combine the odds ratios for mortality using RevMan v5.3. Sensitivity analyses were performed to assess for effect of cell doses.
Results: Mortality was significantly reduced at 12-months in CD34+ vs control subjects [RR = 0.11, (95% CI 0.01, 0.98, p=0.01)]. Autologous CD34+ cell therapy also resulted in an improvement in exercise capacity for both short-term [mean, SD: 73.9s ± 130.0 s(control) vs 137.2s ± 137.2s (CD34+)] and 12-month timepoints [68.4s ± 167.5s (active control) vs 122.2s ± 174.6s (CD34+), Figure 1, p=02]. These results remained significant when confined to patients receiving a dose of 1 x 105 CD34+ cells/kg. Auto-CD34+ cell therapy was associated with a numeric, but not statistically significant, reduction in MACE [RR 0.66 (95% CI 0.32, 1.37)].
Conclusions: Combined analysis of three trials demonstrates statistically significant improvements in mortality and exercise capacity in CD34+ cell therapy treated patients compared with blinded controls, despite a robust placebo effect in exercise capacity. These data point to the need for further development and evaluation of this therapy for this highly symptomatic patient population.
Author Disclosures: T.J. Povsic: Research Grant; Modest; Baxter Healthcare. T.D. Henry: Consultant/Advisory Board; Modest; Baxter Healthcare. E.M. Jolicoeur: None. J.H. Traverse: None. R.A. Schatz: None. A.S. Hunt: Employment; Significant; Baxalta/Shire. D.W. Losordo: Other; Significant; Baxalta US.
- © 2016 by American Heart Association, Inc.