DREAM-HF: MPC therapy for HFrEF did not meet primary endpoint

Transendocardial delivery of mesenchymal precursor cells (MPCs) did not reduce cumulative recurrent non-fatal decompensated heart failure (HF) events in HF patients with a reduced ejection fraction (HFrEF). However, a single dose of MCPs was associated with lower rates of non-fatal myocardial infarction, non-fatal stroke, and cardiac death. These effects were more pronounced in patients with baseline inflammation.

Dr Emerson Perin (Texas Heart Institute, TX, USA) argued that MPCs may decrease cardiac inflammation, reduce heart muscle death, induce a microvascular network in heart muscle, and reverse endothelial dysfunction [1]. In a recent phase 2 trial, MPCs showed promising results in reducing HF-associated events in patients with high-risk, persistent HFrEF [2]. The multicentre, double-blind, sham-controlled, phase 3 DREAM-HF trial (NCT02032004) randomised 537 patients with HFrEF (New York Heart Association [NYHA] functional class II-III) 1:1 to MPC therapy or sham control. Patients in the MPC condition underwent left ventricular electronic mapping to scan for viable but inflamed myocardium. Subsequently, transendocardial injections were administered in the selected myocardial areas. The primary endpoint was the mean cumulative rate of recurrent non-fatal decompensated HF events per 100 patients.

After a mean follow-up of 30 months, the primary endpoint of MPC therapy was not met (HR 1.2; P=0.406). However, predefined secondary endpoints did show benefits of MPC therapy: the risk of non-fatal myocardial infarction or non-fatal stroke was decreased in the MPC group (HR 0.35; P=0.001) and the risk of cardiac death was reduced in NYHA class II patients within the treatment arm (HR 0.43; P=0.044).

In addition, a post-hoc analysis showed that MPC therapy was able to reduce a composite outcome of cardiac death, non-fatal myocardial infarction, or non-fatal stroke in patients with elevated inflammatory markers (hsCRP ≥2 mg/L; HR 0.551; P=0.012) but not in patients without inflammation (hs-CRP <2 mg/L; HR 0.843; P=0.519). Compared with the sham control, MPC therapy was not associated with an increased risk of adverse events. Nor did MPC administration evoke clinically meaningful immune-related responses.

1. 
   
   1. Perin EC, et al. Randomized trial of targeted transendocardial delivery of mesenchymal precursor cells in high-risk chronic heart failure patients with reduced ejection fraction – the DREAM-HF trial. LBS05, AHA Scientific Sessions 2021, 13–15 November.
   2. Perin EC, et al. Circ Res. 2015;117:576–584.

 

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Posted on 14 January 2022