TY - JOUR

T1 - Effect of high-dose mineralocorticoid receptor antagonist eplerenone on urinary albumin excretion in patients with type 2 diabetes and high cardiovascular risk

T2 - Data from the MIRAD trial

AU - Brandt-Jacobsen, Niels H.

AU - Johansen, Marie Louise

AU - Rasmussen, Jon

AU - Forman, Julie L.

AU - Holm, Maria Refsgaard

AU - Faber, Jens

AU - Rossignol, Patrick

AU - Schou, Morten

AU - Kistorp, Caroline

PY - 2021

Y1 - 2021

N2 - Aim: As mineralocorticoid receptor antagonists (MRAs) may possess renoprotective effects in type 2 diabetes (T2D), it was decided to investigate the impact of high-dose MRA on prespecified secondary endpoints—namely, change in urinary albumin–creatinine ratio (UACR) and 24-h ambulatory blood pressure—in the MIRAD trial. Methods: This was a double-blind clinical trial in which T2D patients at high risk of or with established cardiovascular disease (CVD) were randomized to either high-dose (100–200 mg) eplerenone or a dose-matched placebo as an add-on to background antihypertensive treatment for 26 weeks. Safety was evaluated by the incidence of hyperkalaemia and kidney-related adverse events. Results: A total of 140 patients were enrolled (70 in each group). Baseline UACR was 17 mg/g (geometric mean; 95% CI: 13–22); this decreased by 34% in the eplerenone group compared with the placebo group at week 26 (95% CI: −51% to −12%; P = 0.005). There was no significant decrease in 24-h systolic blood pressure (SBP) due to treatment (−3 mmHg; 95% CI: −6 to 1; P = 0.150). However, the observed change in 24-h SBP correlated with the relative change in UACR in the eplerenone group (r = 0.568, P < 0.001). Mean baseline (± SD) estimated glomerular filtration rate (eGFR) was 85 (± 18.6) mL/min/1.73 m2, and 12 (± 9%) had an eGFR of 41–59 mL/min/1.73 m2. No significant differences in the incidence of mild hyperkalaemia (≥ 5.5 mmol/L; eplerenone vs placebo: 6 vs 2, respectively; P = 0.276) and no severe hyperkalaemia (≥ 6.0 mmol/L) were observed. Conclusion: The addition of high-dose eplerenone to T2D patients at high risk of CVD can markedly reduce UACR with an acceptable safety profile.

AB - Aim: As mineralocorticoid receptor antagonists (MRAs) may possess renoprotective effects in type 2 diabetes (T2D), it was decided to investigate the impact of high-dose MRA on prespecified secondary endpoints—namely, change in urinary albumin–creatinine ratio (UACR) and 24-h ambulatory blood pressure—in the MIRAD trial. Methods: This was a double-blind clinical trial in which T2D patients at high risk of or with established cardiovascular disease (CVD) were randomized to either high-dose (100–200 mg) eplerenone or a dose-matched placebo as an add-on to background antihypertensive treatment for 26 weeks. Safety was evaluated by the incidence of hyperkalaemia and kidney-related adverse events. Results: A total of 140 patients were enrolled (70 in each group). Baseline UACR was 17 mg/g (geometric mean; 95% CI: 13–22); this decreased by 34% in the eplerenone group compared with the placebo group at week 26 (95% CI: −51% to −12%; P = 0.005). There was no significant decrease in 24-h systolic blood pressure (SBP) due to treatment (−3 mmHg; 95% CI: −6 to 1; P = 0.150). However, the observed change in 24-h SBP correlated with the relative change in UACR in the eplerenone group (r = 0.568, P < 0.001). Mean baseline (± SD) estimated glomerular filtration rate (eGFR) was 85 (± 18.6) mL/min/1.73 m2, and 12 (± 9%) had an eGFR of 41–59 mL/min/1.73 m2. No significant differences in the incidence of mild hyperkalaemia (≥ 5.5 mmol/L; eplerenone vs placebo: 6 vs 2, respectively; P = 0.276) and no severe hyperkalaemia (≥ 6.0 mmol/L) were observed. Conclusion: The addition of high-dose eplerenone to T2D patients at high risk of CVD can markedly reduce UACR with an acceptable safety profile.

KW - High-dose

KW - Mineralocorticoid receptor antagonist

KW - Type 2 diabetes

KW - Urinary albumin excretion

U2 - 10.1016/j.diabet.2020.08.005

DO - 10.1016/j.diabet.2020.08.005

M3 - Journal article

C2 - 32919068

AN - SCOPUS:85091262066

VL - 47

JO - Diabetes & Metabolism

JF - Diabetes & Metabolism

SN - 1262-3636

IS - 4

M1 - 101190

ER -