麻豆传媒

NEW ORLEANS -- The stem cells that have shown promise for refractory angina maintained their efficacy in a meta-analysis, as researchers once again made their case for a therapy long abandoned by its trial sponsor.

Their latest appeal: A pooling of three small, double-blind trials that randomized patients to CD34+ cell injections (n=187), placebo (n=89), and unblinded standard of care (n=28). Rates of major adverse cardiac events out to 24 months numerically favored CD34+ group (~30% versus ~40% for placebo injections, P=0.08). Deaths did reach statistical difference (~2% versus 12%, P=0.003).

Importantly, event rates were through the roof with open-label standard of care (75%), according to Thomas J. Povsic, MD, PhD, of Duke Clinical Research Institute in Durham, N.C., and colleagues at this year's meeting.

Although the placebo group improved its total exercise time, this metric was consistently around 50 seconds better in the CD34+ cohort (P<0.05 at 3, 6, and 12 months).

"We believe that this type of cell therapy for refractory angina is particularly promising and may improve both functional status and mortality," according to the trialists. "It is imperative to explore methods to bring this therapy to patients."

Lacking, however, is a funding source for clinical translation.

After going through several reorganizations, Baxter halted the RENEW trial in December 2013, reportedly for financial reasons rather than safety or efficacy problems. Povsic's group marched on and reported last year that intramyocardial delivery of CD34+ cells was associated with fewer deaths and better exercise time.

Altogether, patients in the pooled analysis commonly had baseline diabetes (53%), hypertension (87%), hyperlipidemia (84%), and histories of percutaneous coronary intervention (88%) and coronary artery bypass graft surgery (91%).

Close to 90% were on beta blockers; over 80% on nitrates; and 50% on calcium channel blockers, Povsic added.

"It's a shame that individual trials were stopped early. These are desperate patients that don't have any therapy to help them. If I were to be a curmudgeon, however, I would say a 70% reduction in events -- that gets attention, but that's not realistic in an underpowered trial," said session co-moderator Gregg W. Stone, MD, of Columbia University Medical Center/New York-Presbyterian Hospital.

"And that extra minute: how does that translate into quality of life? Is that a meaningful difference?"

Povsic argued that drugs like ranolazine (Renaxa) have been FDA-approved for just 24-45 seconds of extra exercise time -- enhanced external counter pulsation therapy was green-lighted for an improvement of just 16 seconds.

The researcher said it was possible that other companies may want to pick up where Baxter left off to file for expedited FDA approval or explore the regenerative therapies initiative of the 21st Century Cures Act.

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