TY - JOUR

T1 - Mineralocorticoid Receptor Antagonist Improves Cardiac Structure in Type 2 Diabetes

T2 - Data From the MIRAD Trial

AU - Brandt-Jacobsen, Niels H.

AU - Lav Madsen, Per

AU - Johansen, Marie Louise

AU - Rasmussen, Jon J.

AU - Forman, Julie L.

AU - Holm, Maria R.

AU - Rye Jørgensen, Niklas

AU - Faber, Jens

AU - Rossignol, Patrick

AU - Schou, Morten

AU - Kistorp, Caroline

N1 - Publisher Copyright: © 2021 American College of Cardiology Foundation

PY - 2021

Y1 - 2021

N2 - 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)

AB - 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)

KW - cardiovascular risk

KW - fibrosis

KW - left ventricular mass regression

KW - mineralocorticoid receptor antagonist

KW - preserved ejection fraction

KW - type 2 diabetes

U2 - 10.1016/j.jchf.2021.02.016

DO - 10.1016/j.jchf.2021.02.016

M3 - Journal article

C2 - 34325885

AN - SCOPUS:85110604558

VL - 9

SP - 550

EP - 558

JO - J A C C: Heart Failure

JF - J A C C: Heart Failure

SN - 2213-1779

IS - 8

ER -