Effect of mineralocorticoid receptor blocker, esaxerenone, on home blood pressure and albuminuria in japanese hypertensive patients with dkd (ex-dkd study)

Objective: To investigate the effect of esaxerenone on home blood pressure (BP) and albuminuria in Japanese hypertensive patients with diabetic kidney disease (DKD) who had an inadequate response to BP-lowering treatment with a renin angiotensin system (RAS) inhibitor or a RAS inhibitor plus a calcium channel blocker (CCB). Design and method: The EX-DKD study (jRCTs061190027) was a multicenter, open-label study conducted in Japan. The study enrolled hypertensive patients with DKD who had previously received a RAS inhibitor or a RAS inhibitor plus CCB for < 12 weeks, and had sitting office systolic BP (SBP) 130 to < 180 mmHg and/or diastolic BP (DBP) 80 to < 110 mmHg, UACR < 1000 mg/g creatinine, and eGFRcreat 30 to < 60 mL/min/1.73m 2 at baseline. Based on baseline UACR, the patients were divided into 3 subcohorts: UACR < 30, 30 to < 300, and 300 to < 1000 mg/g creatinine. Esaxerenone was incrementally dosed for 12 weeks: 1.25, 2.5, and 5 mg/day at the start of treatment, Week4, and Week8, respectively, based on each patient's condition. The primary efficacy endpoint was change in morning home SBP/DBP from baseline to end of treatment (EOT). Secondary endpoints included the proportion of patients achieving target BP at Week12, change in UACR from baseline to EOT, and safety (including serum potassium level). Results: The baseline characteristics of the overall study population (n = 109) were mean age, 72.6 years; male, 54.1%; morning home SBP/DBP, 135.6/75.9 mmHg; UACR < 30, 30 to < 300, and 300 to < 1000 mg/g creatinine, 41.3%, 37.6%, and 21.1%, respectively; eGFRcreat, 49.4 mL/min/1.73m 2 ; RAS inhibitor, 33.0%; RAS inhibitor plus CCB, 67.0%. Morning home SBP/DBP decreased significantly from baseline to EOT in the total population (-11.6/-5.2 mmHg, both p < 0.001) and all UACR subcohorts (all p < 0.001). Similar results were obtained for bedtime home and office BP. At Week12, 38.5% of the total population had achieved target morning home BP. UACR improved significantly from baseline to EOT in the total population and UACR subcohorts; the overall percentage change was -50.9% (p < 0.001). Incidences of treatment-emergent adverse events (TEAEs) and drug-related TEAEs were 23.2% and 7.1%, respectively. The percentage of patients with serum potassium <5.5 mEq/L during the study period was 2.7%, and no patients had serum potassium < 6.0 mEq/L. Conclusions: Esaxerenone significantly reduced morning home BP as well as bedtime home and office BP and significantly halved albuminuria in Japanese hypertensive patients with DKD. The effects were consistent regardless of their UACR severity without clinically relevant serum potassium elevation.