Efficacy and safety of esaxerenone in hypertensive patients with chronic kidney disease, with or without type 2 diabetes mellitus: a pooled analysis of five clinical studies.

Abstract

Effective management of blood pressure (BP) and albuminuria are crucial for suppressing chronic kidney disease (CKD) progression and cardiovascular risks in hypertension. This pooled analysis evaluated the antihypertensive effects, organ-protective effects, and safety of esaxerenone in hypertensive patients with CKD by integrating five clinical studies of esaxerenone. Patients were divided based on type 2 diabetes mellitus (T2DM) status (with or without T2DM) and creatinine-based estimated glomerular filtration rate (eGFR_creat) (30 to <60 and ≥60 mL/min/1.73 m²). Significant changes in morning home BP from baseline at Week 12 were observed in the overall population (mean change -12.8/ - 5.4 mmHg), T2DM subgroups ( - 12.2/ - 4.5 and -14.5/ - 7.8 mmHg), and eGFR_creat subgroups ( - 12.5/ - 4.7 and -14.0/ - 6.9 mmHg) (all P < 0.001). Bedtime home and office BP showed similar tendencies. Urine albumin-to-creatinine ratio significantly improved from baseline at Week 12 in the overall population (mean change: -55.2%), T2DM subgroups ( - 56.5% and -52.0%), and eGFR_creat subgroups ( - 54.6% and -55.4%) (all P < 0.001). N-terminal pro-B-type natriuretic peptide levels significantly decreased in the overall population (percent change: -14.1%) and subgroup without T2DM ( - 25.3%). The incidence of serum potassium ≥5.5 mEq/L was lower in the subgroup with T2DM vs without T2DM (3.1% and 11.3%), potentially related to the use of sodium-glucose cotransporter 2 inhibitors. These findings highlight the sustained BP-lowering effect of esaxerenone throughout the day in hypertensive patients with CKD, irrespective of T2DM status, and its significant reduction in albuminuria. The data support the safety and efficacy of esaxerenone in this patient population, underscoring its potential as a valuable therapeutic option. This study showed that esaxerenone significantly lowered morning home, bedtime home, and office BP and UACR in hypertensive patients with CKD, regardless of T2DM status and kidney function (eGFR), and without any novel safety concerns. These highlight the efficacy, organ-protective effects, and safety of esaxerenone in hypertensive patients with CKD.