Elsevier

JACC: Heart Failure

Volume 9, Issue 8, August 2021, Pages 550-558
JACC: Heart Failure

Heart Failure and Diabetes Special Issue
Clinical Research
Mineralocorticoid Receptor Antagonist Improves Cardiac Structure in Type 2 Diabetes: Data From the MIRAD Trial

https://doi.org/10.1016/j.jchf.2021.02.016Get rights and content
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Abstract

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)

Key Words

cardiovascular risk
fibrosis
left ventricular mass regression
mineralocorticoid receptor antagonist
preserved ejection fraction
type 2 diabetes

Abbreviations and Acronyms

cLMM
constrained linear mixed model
CMR
cardiac magnetic resonance
CO
cardiac output
CVD
cardiovascular disease
EDV
end-diastolic volume
eGFR
estimated glomerular filtration rate
ESV
end-systolic volume
HF
heart failure
HFrEF
heart failure with reduced ejection fraction
LVEF
left ventricular ejection fraction
LVM
left ventricular mass
LVMi
left ventricular mass indexed
MI
myocardial infarction
MR
mineralocorticoid receptor
MRA
mineralocorticoid receptor antagonist
NT-proBNP
N-terminal pro–B-type natriuretic peptide
P1NP
procollagen type I N-terminal propeptide
P3NP
procollagen type III N-terminal propeptide
RAS-I
renin-angiotensin-system inhibitor
SV
stroke volume
uACR
urine-albumin-creatinine ratio

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