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Eplerenone Reduces Cardiac Mass in Type 2 Diabetes
Quick Takes
- High-dose eplerenone (100-200 mg) in high-risk type 2 diabetes (and estimated glomerular filtration rate >82 ml/min/1.73 m2) was associated with a clear reduction in LV mass and in NT-proBNP and P1NP levels.
- Mineralocorticoid receptor antagonists (MRAs) favorably impact cardiac remodeling independent of blood pressure.
- The next step would be to conduct long-term studies to determine whether MRAs in patients with type 2 diabetes favorably impact heart failure outcomes and prevent heart failure.
Study Questions:
What is the impact of the mineralocorticoid receptor antagonist (MRA) eplerenone on left ventricular mass (LVM) in type 2 diabetes patients at high risk for cardiovascular disease (CVD)?
Methods:
The study authors conducted the MIRAD (Mineralocorticoid Receptor Antagonists in Type 2 Diabetes) trial to investigate the cardiac and metabolic effects of high-dose eplerenone in a high-risk type 2 diabetes cohort—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 (100-200 mg) or placebo as an add-on to standard care for 26 weeks. They analyzed prespecified secondary endpoints of LVM and results of myocardial fibrosis as measured by cardiac magnetic resonance (CMR) imaging and circulating markers of cardiac function and fibrosis. Indexed left ventricular mass (LVMi) and T1 time (fibrotic load) were measured using 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 the 140 patients in the study cohort, 104 patients were subject to CMR imaging (eplerenone: 54 patients; placebo: 50 patients). Mean LVMi at baseline was 74.2 ± 16 g/m2. A decrease in LVMi from baseline to week 26 was observed in patients taking eplerenone of 4.7 g/m2 (95% confidence interval [CI], -6.9 to -2.5; p < 0.001), whereas no change was observed in the placebo group (-1.0 g; 95% CI, -3.3 to 1.2; p = 0.374). The estimated treatment effect (i.e., 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 study authors concluded that addition of high-dose eplerenone in high-risk type 2 diabetes was associated with a clear reduction in LVM and in NT-proBNP and P1NP levels, which may suggest a clinical benefit in heart failure prevention.
Perspective:
This is an important study because it suggests that MRAs favorably impact cardiac remodeling independent of blood pressure. The next step would be to conduct long-term studies to determine whether MRAs in patients with type 2 diabetes favorably impact heart failure outcomes and prevent heart failure.
Clinical Topics: Anticoagulation Management, Diabetes and Cardiometabolic Disease, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: Biomarkers, Blood Pressure, Blood Pressure Determination, Collagen Type I, Diabetes Mellitus, Type 2, Fibrosis, Geriatrics, Heart Failure, Magnetic Resonance Spectroscopy, Metabolic Syndrome, Mineralocorticoid Receptor Antagonists, Natriuretic Peptide, Brain, Peptide Fragments, Primary Prevention, Ventricular Remodeling
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