Effect of high-dose mineralocorticoid receptor antagonist eplerenone on urinary albumin excretion in patients with type 2 diabetes and high cardiovascular risk: Data from the MIRAD trial

Research output: Contribution to journalJournal articlepeer-review

  • Niels H. Brandt-Jacobsen
  • Marie Louise Johansen
  • Jon Rasmussen
  • Forman, Julie Lyng
  • Maria Refsgaard Holm
  • Jens Faber
  • Patrick Rossignol
  • Morten Schou
  • Caroline Kistorp

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.

Original languageEnglish
Article number101190
JournalDiabetes and Metabolism
Volume47
Issue number4
Number of pages7
ISSN1262-3636
DOIs
Publication statusPublished - 2021

    Research areas

  • High-dose, Mineralocorticoid receptor antagonist, Type 2 diabetes, Urinary albumin excretion

ID: 254468680