Effects of esaxerenone add-on therapy versus angiotensin II receptor blocker dose escalation on albuminuria and blood pressure in hypertensive patients with type 2 diabetes: An exploratory randomized study.

Abstract

Aims: Residual albuminuria remains a major clinical challenge in patients with type 2 diabetes mellitus and hypertension despite renin-angiotensin system inhibitor therapy. Esaxerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, reduces albuminuria; however, its effects on oxidative stress remain unclear.

Materials and methods: This 24-week, prospective, randomized, open-label, multicenter exploratory trial was conducted in Japan. Hypertensive patients with type 2 diabetes mellitus and albuminuria receiving standard-dose angiotensin II receptor blocker therapy were randomized to angiotensin II receptor blocker dose escalation or esaxerenone add-on therapy. Of 50 randomized patients, 47 were included in the full analysis set and 39 in the final analysis population (20 in the angiotensin II receptor blocker dose-escalation group and 19 in the esaxerenone add-on group). The primary endpoints were changes from baseline to Week 24 in urinary albumin-to-creatinine ratio and oxidative stress assessed by diacron-reactive oxygen metabolites.

Results: Esaxerenone add-on therapy produced a significantly greater reduction in log-transformed urinary albumin-to-creatinine ratio than angiotensin II receptor blocker dose-escalation therapy, with an adjusted between-group ratio of 0.71 (95% confidence interval, 0.58-0.87; p = 0.002). Systolic and diastolic blood pressures were significantly lower with esaxerenone. Estimated glomerular filtration rate decreased more with esaxerenone, whereas serum potassium levels did not differ significantly between groups. No significant between-group difference was observed in diacron-reactive oxygen metabolites.

Conclusions: In hypertensive patients with type 2 diabetes mellitus and albuminuria, esaxerenone add-on therapy reduced albuminuria and blood pressure more effectively than angiotensin II receptor blocker dose escalation but did not significantly reduce oxidative stress.