Stem Cell Therapy for Heart Failure Reduces CV Events, Death in Select Patients—but Not Hospitalization

Precision medicine in heart failure? For select patients, notably those with high levels of inflammation, a study using stem cells injected into the heart could offer promise—but the study fell short in a key measure important to payers.

The DREAM-HF trial presented Sunday at the 2021 American Heart Association (AHA) Scientific Sessions demonstrated benefits for certain patients with chronic heart failure (HF), but the results showed no difference in the rate of hospitalization, an indicator that helps drive evaluations of cost-effectiveness. Hospitalization for HF is costs Medicare $11 billion a year, according to a 2018 study published by the AHA’s journal Circulation.

The study examined the use of mesenchymal precursor cells (MPCs), which were injected into the heart to target inflammation and treat the worst cases of chronic HF—on top of what can be achieved with guideline-directed medication. The hope was that a single injection of healthy stem cells from a donor would reduce the number of trips to the hospital and the number of major cardiovascular (CV) events, such as heart attacks or strokes.

Lead study author Emerson C. Perin, MD, PhD, who is director of the Center for Clinical Research and medical director of the Texas Heart Institute in Houston, described MPS as “allogeneic STRO-1/STRO-3+ cells that are immunoselected from adult human bone marrow mononuclear cell populations.” Preclinical studies suggest that MPCs had anti-inflammatory effects and were “proangiogenic,” meaning they promote vascular endothelial growth factor (VEGF). The first use of these cells in humans occurred in 2006 in Australia, Perin said. The idea behind MPCs is that they will reduce inflammation, restore capillary function in the heart muscle, and reduce endothelial dysfunction.

The stem cell treatment did reduce non-fatal heart attack and strokes by 65%, and reduced CV death. However, results showed the procedure did not reduce hospitalizations. In addition, the treatment had its most marked effects in particular groups of HF patients: those with elevated inflammation who met criteria for NY Heart Association (NYHA) Class II for heart failure with reduced ejection fraction (HFrEF), which meant their hearts had less severe damage. For these patients, CV death was reduced 80%.

“Cell therapy has the potential to change how we treat heart failure,” lead study author Emerson C. Perin, MD, PhD, who is director of the Center for Clinical Research and medical director of the Texas Heart Institute in Houston, said in a statement. “This study addresses the inflammatory aspects of heart failure, which go mostly untreated, despite significant pharmaceutical and device therapy development. Our findings indicate stem cell therapy may be considered for use in addition to standard guideline therapies.”

Using traditional end points from HF studies may have been a limiting factor, Perin said. Such end points do not fully measure the benefits or mechanisms of the stem cells and their value in preventing heart attack or stroke.

DREAM-HF Results

Formally called the “Randomized Trial of Targeted Transendocardial Delivery of Mesenchymal Precursor Cells in High-Risk Chronic Heart Failure Patients with Reduced Ejection Fraction,” DREAM-HF trial treated 537 patients, with an average age of 63. Only 20% were women. All were NYHA Class II or Class III. In this study, 261 patients received MPCs and 276 received a sham procedure. Patients were discharged the next day and followed for 30 months. Results showed:

• The trial did not meet its primary end point, which compared the mean cumulative rate of recurrent non-fatal compensated HF events per 100 patients. In the intent-to-treat population of 565 patients, the hazard ratio (HR) was 1.2 (95% CI: 0.8-1.7, P = .406).
• For reduction of risk of non-fatal heart attack or non-fatal stroke, results favored the stem cell treatment, with HR 0.346 (95% CI: 0.180-0.664, P = .001). Among NYHA Class II patients, the HR was 0.336 (95% CI: 0.122-0.923, P = .035).
• Reduced risk of cardiac death was pronounced among NYHA Class II patients, with HR .443 (95% CI: 0.191-0.979, P = .044). There was virtually no difference for NYHA Class III patients, with HR 1.180 (95% CI: 0.778-1.886, P = .490).
• In a composite of time to first event among patients with elevated inflammation were combined, results markedly favored with elevated inflammation, who saw a 45% reduced risk of time to first-event for cardiac death or non-fatal heart attack or stroke (HR 0.551, 95% CI: 0.345-0.876, P = .012). There was no statistical difference for those without elevated inflammation, which was defined as high-sensitivity C-reactive protein of ≥2 mg/L.

In response to a question, Perin said there were plenty of reasons to be excited about the study, despite it missing its primary end point. “This is the largest study in cell therapy that's ever been performed [in heart failure], and with a very long follow up—a mean of 30 months.”

The results seen among patients with higher levels of inflammation are very important, he said. The distinct difference among patients with elevated levels of inflammation and those without is consistent with what is known about its role in cardiac inflammation and persistent heart failure.

DREAM-HF, he said, demonstrates the ability of a non-inflammatory mechanism to have a “cause and effect” benefit in HF. “The stem cells acted locally in the heart, and they also helped in blood vessels throughout the body,” he said.