ANTIHYPERTENSIVE EFFECTS AND SAFETY OF ESAXERENONE IN HYPERTENSIVE PATIENTS WITH MODERATE KIDNEY DYSFUNCTION

Abstract

Objective: Mineralocorticoid receptor blockers (MRB) adding to renin–angiotensin system (RAS) inhibitors should be an effective treatment option for the strict blood pressure (BP) control of the hypertensive patients with moderate kidney dysfunction. Esaxerenone is a novel, first non-steroidal MRB with a dose-dependent antihypertensive effect and renal protective potential. We investigated the efficacy and safety of esaxerenone in Japanese hypertensive patients with moderate kidney dysfunction. Design and method: Two multicenter, open-label, non-randomized, dose-escalation studies were conducted to assess the efficacy and safety of esaxerenone monotherapy and add-on therapy to RAS inhibitor. Esaxerenone therapy started from 1.25 mg/day, titrated to 5 mg/day and continued until 12 weeks. Primary endpoint was change from baseline in sitting BP. Safety, pharmacokinetics, and urinary albumin-to-creatinine ratios were also evaluated. Results: Of 91 patients, 33 received monotherapy and 58 received add-on therapy; mean baseline estimated glomerular filtration rates were 52 and 51 mL/min/1.73m2, respectively. The esaxerenone dose was increased to 2.5 mg/day and above in 100% (n = 33) and 93% (n = 54) of patients receiving monotherapy and add-on therapy, respectively. After the initiation of treatment, significant reduction in sitting SBP/DBP at the end of treatment was observed in both studies (monotherapy: 19/9 mmHg; add-on therapy: 18/8 mmHg; both P < 0.001); 64% and 48% of patients achieved target blood pressure (<140/90 mmHg). The antihypertensive effects were consistent across patient subgroups by age, BMI, and eGFR. The UACR decreased significantly from baseline to Week 12: by 26% in the monotherapy study (P < 0.01) and 29% in the add-on therapy study (P < 0.001). An increased serum K+ level of 5.5 mEq/L and above occurred in 7 patients (12%) receiving add-on therapy, but in none receiving monotherapy. All increases in serum K+ were transient and no patient met predefined serum K+ level criteria for dose reduction or therapy discontinuation. No patient discontinued treatment due to kidney function decline. Conclusions: Esaxerenone demonstrated sufficient antihypertensive effects and was well tolerated in hypertensive patients with moderate kidney dysfunction, both as monotherapy and add-on therapy to a RAS inhibitor.