Mesenchymal precursor cell therapy fails to lower HF events, but may confer other benefits
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In the DREAM-HF trial, mesenchymal precursor cell therapy did not meet the primary endpoint of improvement in recurrent nonfatal decompensated HF events, but did reduce risk for nonfatal MI or stroke in certain patients with HF.
Results from the trial of 537 patients with persistent HF with reduced ejection fraction on maximal guideline-directed medical therapy (mean age, 63 years; 80% men) randomly assigned to treatment with mesenchymal precursor cells (Mesoblast) injected into the heart muscle during a catheter-based procedure or to a sham procedure were presented at the American Heart Association Scientific Sessions.
“Unfortunately, because the trial did not meet its primary endpoint, the very important novel findings did not receive the attention that I believe it merited,” Cardiology Today Chief Medical Editor Carl J. Pepine, MD, MACC, professor of medicine at the University of Florida, said in an interview. Pepine was a site principal investigator for the trial.
In the intention-to-treat population of 565 patients, 28 of whom did not undergo a procedure due to protocol violations, the primary outcome of mean cumulative rate of recurrent nonfatal decompensated HF events per 100 patients did not differ between those assigned mesenchymal precursor cell therapy and those assigned the sham procedure at a mean follow-up of 29.9 months (HR = 1.2; 95% CI, 0.8-1.7; P = .406), Emerson C. Perin, MD, PhD, medical director at Texas Heart Institute, said during a press conference.
However, Perin said, the cell therapy group had lower rates of nonfatal MI or stroke compared with the sham group (4.6% vs. 13%; HR = 0.346; 95% CI, 0.18-0.664; P = .001), which was true regardless of whether patients had NYHA class II HF (5% vs. 14.2%; HR = 0.336; 95% CI, 0.122-0.923; P = .035) or NYHA class III HF (4.3% vs. 12.4%; HR = 0.351; 95% CI, 0.149-0.827; P = .017).
Risk for cardiac death was similar between the groups in the overall cohort, but among patients with NYHA class II HF, it was lower in the cell therapy group (8% vs. 19.8%; HR = 0.433; 95% CI, 0.191-0.979; P = .044), Perin said at the press conference.
The outcome of time to first event of cardiac death, nonfatal MI and nonfatal stroke favored the cell therapy group (HR = 0.667; 95% CI, 0.472-0.941; P = .021), but the treatment effect was much greater in those with high-sensitivity C-reactive protein 2 mg/L or greater (HR = 0.551; 95% CI, 0.346-0.876; P = .012) than in those without it (HR = 0.843; 95% CI, 0.48-1.448; P = .519), according to the researchers.
Perin said during the press conference that “we know where the benefits of the cells are; that’s identified in the patients with inflammation. We know that if patients aren’t inflamed, this therapy really isn’t going to help them.”
“These provocative new findings support the suggestion that although the cells were injected into heart muscle, they had important vascular anti-inflammatory actions at a distance,” Pepine told Healio. “This concept of effects on blood vessels at a distance from their heart muscle site of injection is also consistent with findings from two randomized trials with the same cells given to patients receiving left ventricular assist devices. In those trials, the cells reduced the frequency of gastrointestinal bleeding. This new knowledge should stimulate new trials with intravenous injections of allogeneic mesenchymal stem cells for conditions where inflammation/immune activation is a key mechanism.”
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Perin EC, et al. LBS.05. Building on the Foundations of Treatment: Advances in Heart Failure Therapy. Presented at: American Heart Association Scientific Sessions; Nov. 13-15, 2021 (virtual meeting).
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