Stem Cells Did Not Decrease Heart Failure Readmissions in DREAM-HF

Key Points:

• In the DREAM-HF study, patients with persistent NYHA II-III HFrEF were treated with transendocardial mesenchymal precursor cells (MPCs) or a sham procedure. The primary outcome was a mean cumulative rate of recurrent non-fatal decompensated HF events. Pre-specified secondary analyses included evaluation of non-fatal MI or non-fatal stroke and cardiac death; post—hoc analyses included time to first event for cardiac death or non-fatal MI/stroke, as well as cardiac death alone, stratified by baseline CRP.
• Treatment with MPCs did not reduce the primary endpoint, but MPC administration did significantly reduce non-fatal MI or non-fatal stroke, cardiac death in NYHA II but not III patients, and a composite of cardiac death, non-fatal-MI, and non-fatal stroke (which appeared to be largely driven by patients with elevated baseline CRP).

Patients with severe chronic, persistently symptomatic heart failure with reduced ejection fraction have limited advanced treatment options. Preclinical studies have suggested that mesenchymal precursor cells (MPCs), allogenic stem cells which are immunoselected from mononuclear bone marrow cell populations, may have anti-inflammatory and proangiogenic effects in both ischemic and non-ischemic HF models. The first MPCs were injected via a transendocardial procedure in ischemic cardiomyopathy in 2006. In a breaking presentation at the 2021 American Heart Association Scientific Sessions today, Dr. Emerson Perin (Texas Heart Institute, Houston) and his team presented the results of the Efficacy and Safety of Allogeneic Mesenchymal Precursor Cells (Rexlemestrocel-L) for the Treatment of Heart Failure (DREAM HF-1) trial.

The DREAM-HF study (NCT02032004) was a multicenter, randomized, double-blinded sham-controlled randomized trial, conducted at 59 centers across the United States and Canada. Patients were treated with either MPCs or a sham injection. All recruited patients were required to have chronic ischemic or non-ischemic HF of at least 6 months duration, LVEF ≤40%, NYHA II-III symptoms, and stabilization on optimally tolerated GDMT for at least 1 month prior to randomization. Some relevant exclusion criteria included acute MI or unstable angina within 1 month, any coronary or arterial revascularization procedure within 2 months, and moderate to severe aortic stenosis.

A total of 537 patients were randomized; 261 received transendocardial MPCs and 276 received a sham control procedure. The average EF was ~28%. Patients were followed for at least 6 months. The primary outcome was a mean cumulative rate of recurrent non-fatal decompensated HF events per 100 patients, which was not significantly different between the groups. Pre-specified secondary analyses included evaluation of non-fatal MI or non-fatal stroke, and cardiac death. Post-hoc, the investigators determined time to first event for cardiac death or non-fatal MI/stroke, as well as cardiac death alone, as compared between patients with elevated CRP (≥2mg/L) or without. MPC administration resulted in a 65% reduction in risk of non-fatal MI or non-fatal stroke across all patients (p=0.001), as well as both NYHA II and NYHA III subgroups. Similarly, MPCs resulted in a 57% reduction in cardiac death in NYHA II patients (p=0.044), but not in the total population or NYHA III patients. MPC treatment resulted in reduced time to first event for cardiac death or non-fatal MI/stroke in patients (33% reduction, p=0.021), which appeared to be entirely driven by patients with baseline elevated CRP (45% reduction, p=0.012). There were no relevant safety events, except one incidence of LV perforation during LV mapping.

When discussing the implications of the study at the AHA, Dr. Perin stated: “MPCs did not reduce [the primary endpoint] in patients with persistent HFrEF….however, over a median follow-up of 30 months, a single administration of MPCs in addition to GDMT significantly reduced non-fatal MI or non-fatal stroke, cardiac death in NYHA II but not III patients, and a composite of cardiac death, non-fatal-MI, and non-fatal stroke. The benefits of MPC therapy were most evident in patients with baseline inflammation.”