Mineralocorticoid Receptor Antagonist Improves Cardiac Structure in Type 2 Diabetes: Data From the MIRAD Trial

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

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)

TidsskriftJACC: Heart Failure
Udgave nummer8
Sider (fra-til)550-558
Antal sider9
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
Supported by Danish Heart Foundation grant 15-R99-A5855; Danish Diabetes Academy; Herlev Hospital Research Foundation; Danish Medical Association Research Foundation; Gangsted Foundation grant R572-A38190; and Foundation for the Promotion of Medicine AP-Møller. The funders had no role in the design and conduct of the trial, analysis of data, or writing of the manuscript. Dr Kristorp has served on scientific advisory panels and received speaker fees from Boehringer Ingelheim, Merck Sharpe and Dome, AstraZeneca, Amgen, Novartis, Novo Nordisk, and Shire. Dr Rossignol is a consultant for Idorsia, Novartis, Relypsa, AstraZeneca, G3P(stocks), Grünenthal, Stealth Peptides, Fresenius, Sequana Medical, Vifor Fresenius Medical Care Renal Pharma, and Vifor; and is cofounder of Cardiorenal. Dr Forman has served on scientific advisory boards at Merck Sharpe and Dome, AstraZeneca, Novo Nordisk. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Publisher Copyright:
© 2021 American College of Cardiology Foundation

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