Effect On Cardiac Function Among Patients With Type 2 Diabetes Following High-Dose Mineralocorticoid Receptor Antagonist Using Echocardiography; Data From The MIRAD Randomized Clinical Trial

Background: Early heart failure (HF)-prevention is central in patients with type 2 diabetes, and mineralocorticoid receptor antagonists (MRAs) have shown to improve prognosis. We investigated the effect of high-dose MRA, eplerenone, on cardiac function and structure in patients with type 2 diabetes and established or increased risk of cardiovascular disease but without HF. Methods: In the current randomized, placebo-controlled clinical trial, 140 patients with high-risk type 2 diabetes were randomized to high-dose eplerenone (100-200 mg daily) or placebo as add-on to standard care for 26 weeks. Left ventricular (LV) systolic and diastolic function, indexed LV mass (LVMi), and global longitudinal strain (GLS) were assessed using echocardiography at baseline and after 26 weeks of treatment. Results: Of the included patients, 138 (99%) had an echocardiography performed at least once. Baseline early diastolic in-flow velocity (E-wave) indexed by mitral annulus velocity (e’) was mean (SD) 11.1 (0.5), with 31% of patients reaching above 12. No effect of treatment on diastolic function was observed measured by E/e’ (0.0, 95%CI [-1.2 to 1.2], P=0.992) or E/A (-0.1, 95%CI [-0.2 to 0.0], P=0.191). Mean LV ejection fraction (LVEF) at baseline was 59.0% (8.0). No improvement in systolic function was observed when comparing groups after 26 weeks (LVEF: 0.9, 95%CI [-1.1 to 2.8], P=0.382; GLS: -0.4%, 95%CI [-1.5 to 0.6], P=0.422), nor in LVMi (-3.8 g/m2 95%CI [-10.2 to 2.7], P=0.246). Conclusion: In the present echo sub-study, no change in cardiac function was observed following high-dose MRA therapy in patients with high-risk type 2 diabetes. Trial registration: Date of registration 25/08/2015 (EudraCT number: 2015-002519-14)