Objectives

This study investigated the impact of the MR antagonist (MRA) eplerenone on LVM in type 2 diabetes patients at high risk for cardiovascular disease (CVD).

Background

MRA activation is associated with cardiac fibrosis and increased left ventricular mass (LVM), which is an independent predictor of adverse CVD, including heart failure in patients with type 2 diabetes.

Methods

A prespecified analysis of secondary endpoints in a randomized, double-blinded clinical trial of 140 patients with type 2 diabetes at high risk of or established CVD. Patients were randomized to receive high-dose eplerenone therapy (100 mg–200 mg) or placebo as an add-on to standard care for 26 weeks. Indexed LVM (LVMi) and T1 time were measured using cardiac magnetic resonance (CMR) imaging. Biomarkers included N-terminal pro–B-type natriuretic peptide (NT-proBNP), pro-collagen type I N-terminal propeptide (P1NP), and type III N-terminal propeptide (P3NP).

Results

Of 140 patients in the MIRAD trial, 104 patients were subject to CMR imaging (eplerenone: 54 patients; placebo: 50 patients). Mean LVMi at baseline was 74.2 ± 16 g/m². The treatment effect (ie, between-group differences) was a decrease of 3.7 g/m² following the eplerenone treatment (95% CI: −6.7 to −0.7; P = 0.017), with a corresponding decrease in absolute LVM. Plasma NT-proBNP concentrations decreased by 22% (P = 0.017) using eplerenone compared with placebo, and P1NP decreased 3.3 ng/mL (P = 0.019). No differences in T1 times or P3NP concentrations were observed between groups.

Conclusions

The addition of high-dose eplerenone in high-risk type 2 diabetes was associated with a clear reduction in LVMi and in NT-proBNP and P1NP levels, which may suggest a clinical benefit in heart failure prevention. (EU Clinical trials: Mineralocorticoid Receptor Antagonists in Type 2 Diabetes [MIRAD]; 2015-002519-14)

中文翻译：

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盐皮质激素受体拮抗剂改善 2 型糖尿病的心脏结构

目标

本研究调查了 MR 拮抗剂 (MRA) 依普利酮对心血管疾病 (CVD) 高危 2 型糖尿病患者 LVM 的影响。

背景

MRA 激活与心脏纤维化和左心室质量 (LVM) 增加有关，这是不良 CVD 的独立预测因子，包括 2 型糖尿病患者的心力衰竭。

方法

一项对 140 名 2 型糖尿病高危或已确诊 CVD 患者的随机、双盲临床试验中次要终点的预设分析。患者随机接受高剂量依普利酮治疗（100 mg–200 mg）或安慰剂作为标准治疗的附加治疗 26 周。使用心脏磁共振 (CMR) 成像测量索引 LVM (LVMi) 和 T1 时间。生物标志物包括 N 端 B 型利钠肽原 (NT-proBNP)、胶原 I 型 N 端前肽 (P1NP) 和 III 型 N 端前肽 (P3NP)。

结果

在 MIRAD 试验的 140 名患者中，104 名患者接受了 CMR 成像（依普利酮：54 名患者；安慰剂：50 名患者）。基线时的平均 LVMi 为 74.2 ± 16 g/m ²。治疗效果（即组间差异）是依普利酮治疗后降低 3.7 g/m ²（95% CI：-6.7 至 -0.7；P = 0.017），绝对 LVM 相应降低。与安慰剂相比，使用依普利酮后血浆 NT-proBNP 浓度降低了 22% (P = 0.017)，P1NP 降低了 3.3 ng/mL (P = 0.019)。组间未观察到 T1 时间或 P3NP 浓度的差异。

结论

在高危 2 型糖尿病中添加大剂量依普利酮与 LVMi 以及 NT-proBNP 和 P1NP 水平的明显降低相关，这可能表明预防心力衰竭的临床益处。（欧盟临床试验：2 型糖尿病中的盐皮质激素受体拮抗剂 [MIRAD]；2015-002519-14）