Center for Clinical Research, The Texas Heart Institute, Houston, Texas, USA.
Borow Consulting Group LLC, Bryn Mawr, Pennsylvania, USA.
J Am Coll Cardiol. 2023 Mar 7;81(9):849-863. doi: 10.1016/j.jacc.2022.11.061.
Mesenchymal precursor cells (MPCs) are allogeneic, immunoselected cells with anti-inflammatory properties that could improve outcomes in heart failure with reduced ejection fraction (HFrEF).
This study assessed the efficacy and safety of MPCs in patients with high-risk HFrEF.
This randomized, double-blind, multicenter study evaluated a single transendocardial administration procedure of MPCs or sham-control in 565 intention-to-treat patients with HFrEF on guideline-directed therapies. The primary endpoint was time-to-recurrent events caused by decompensated HFrEF or successfully resuscitated symptomatic ventricular arrhythmias. Hierarchical secondary endpoints included components of the primary endpoint, time-to-first terminal cardiac events, and all-cause death. Separate and composite major adverse cardiovascular events analyses were performed for myocardial infarction or stroke or cardiovascular death. Baseline and 12-month echocardiography was performed. Baseline plasma high-sensitivity C-reactive protein levels were evaluated for disease severity.
The primary endpoint was similar between treatment groups (HR: 1.17; 95% CI: 0.81-1.69; P = 0.41) as were terminal cardiac events and secondary endpoints. Compared with control subjects, MPCs increased left ventricular ejection fraction from baseline to 12 months, especially in patients with inflammation. MPCs decreased the risk of myocardial infarction or stroke by 58% (HR: 0.42; 95% CI: 0.23-0.76) and the risk of 3-point major adverse cardiovascular events by 28% (HR: 0.72; 95% CI: 0.51-1.03) in the analysis population (n = 537), and by 75% (HR: 0.25; 95% CI: 0.09-0.66) and 38% (HR: 0.62; 95% CI: 0.39-1.00), respectively, in patients with inflammation (baseline high-sensitivity C-reactive protein ≥2 mg/L).
The primary and secondary endpoints of the trial were negative. Positive signals in prespecified, and post hoc exploratory analyses suggest MPCs may improve outcomes, especially in patients with inflammation.
间充质前体细胞（MPCs）是同种异体免疫选择细胞，具有抗炎特性，可改善射血分数降低的心力衰竭（HFrEF）患者的预后。
本研究评估 MPCs 在高危 HFrEF 患者中的疗效和安全性。
这是一项随机、双盲、多中心研究，共纳入 565 例接受指南指导的治疗后仍有 HFrEF 的患者，按意向治疗原则，评估单次经心内膜 MPCs 或假对照细胞移植的效果。主要终点是由心力衰竭失代偿或成功复苏的有症状室性心律失常引起的复发性事件的时间。分层次要终点包括主要终点的组成部分、首次终末心脏事件时间和全因死亡。分别和联合进行心肌梗死或卒中或心血管死亡的主要不良心血管事件分析。进行基线和 12 个月的超声心动图检查。评估基线时血浆高敏 C 反应蛋白水平以判断疾病严重程度。
治疗组之间的主要终点无差异（HR：1.17；95%CI：0.81-1.69；P=0.41），终末心脏事件和次要终点也无差异。与对照组相比，MPCs 使左心室射血分数从基线增加到 12 个月，在有炎症的患者中效果更明显。MPCs 使心肌梗死或卒中风险降低 58%（HR：0.42；95%CI：0.23-0.76），3 点主要不良心血管事件风险降低 28%（HR：0.72；95%CI：0.51-1.03），在分析人群（n=537）中，使炎症患者（基线时高敏 C 反应蛋白≥2mg/L）的心肌梗死或卒中风险降低 75%（HR：0.25；95%CI：0.09-0.66）和 38%（HR：0.62；95%CI：0.39-1.00）。
试验的主要和次要终点均为阴性。预设和事后探索性分析中的阳性信号表明，MPCs 可能改善预后，尤其是在有炎症的患者中。
