ORLANDO — Intramyocardial delivery of CD34+ cells to patients with refractory angina is tied to fewer deaths and less frequent angina, a study found, even though it was terminated early by the sponsor for business reasons.
At 6 months, the frequency of angina was lower in cell-treated patients (relative risk 0.57, 95% confidence interval 0.36-0.92).
By 2 years, the rate of mortality was reduced in this group as well (3.7% versus 10% for placebo versus 7.1% for standard of care). Both placebo- and CD34+ cell-treated participants showed 1- to 2-minute improvements in exercise time during this period, according to Timothy D. Henry, MD, of Cedars-Sinai Heart Institute in Los Angeles, at the annual meeting of the Society for Cardiovascular Angiography and Interventions (SCAI).
“Cell therapy appears to be a promising approach for these patients who have few options,” said Henry in a press release. “Our results were consistent with phase II results from the ACT34 trial.”
Rates of major adverse cardiovascular events were highest in the standard of care group (68%) when compared with that of placebo and CD34+ recipients (43% and 46%, respectively).
Given that even placebo-treated patients did better than the standard of care cohort in this regard, William W. O’Neill, MD, a panelist at the SCAI session, pointed out the psychological power of optimism. “We need to have hope for our patients. The last thing they want to hear is ‘there’s no hope,’” he said.
Indeed, “patients with standard of care did very poorly,” Henry commented at the SCAI presentation.
Another discussant agreed: “It’s clear that standard of care is not good enough. We know that doing more helps our patients…. Standard of care should not be the standard,” the panelist concluded.
The RENEW study was a phase III trial that enrolled 112 class III and IV angina patients before Baxter pulled the plug in December 2013 (for financial reasons). Individuals were randomized to open-label standard of care, blinded placebo, or CD34+ cell treatment.
“Premature curtailment of RENEW precluded full assessment of CD34+ therapy. Comparison with both standard of care and placebo suggests that intramyocardial CD34+ therapy improves mortality, ex time, and angina to an extent similar to ACT34 and is a promising therapy for refractory angina patients,” Henry emphasized.
“I would call RENEW opportunity lost,” Henry said. “The trial was working extremely well … As investigators, we are extremely frustrated.”
“It is unfortunate the early termination of this study precludes a full evaluation of the efficacy of this therapy for these patients with very few options,” agreed co-investigator Thomas J. Povsic, MD, of Duke University School of Medicine in Durham, in a press release.
“Studies like RENEW are critical to developing reliable and effective cellular therapies for heart patients, and continued funding is essential to advancing the work that this study began. We need to find a way to bring these therapies to patients as quickly and safely as possible.”
The trial was sponsored by Baxter.
Henry disclosed no relevant conflicts of interest.
Society for Cardiovascular Angiography and Interventions
Henry TD, et al "Final results for the RENEW trial: a phase 3, randomized, double blinded, active-controlled, unblinded standard of care study assessing the efficacy and safety of intramyocardial autologous CD34+ cell administration in patients with refractory angina" SCAI 2016.