Efficacy and safety of esaxerenone versus angiotensin II receptor blockers in older patients with hypertension, with and without type 2 diabetes mellitus: a predefined subgroup analysis of the ESCORT-HT study

Abstract This predefined subgroup analysis of the ESCORT-HT study evaluated the antihypertensive efficacy, organ-protective effects, and safety profile of esaxerenone compared with an angiotensin II receptor blocker (ARB) in patients aged ≥65 years with hypertension on amlodipine, stratified by the presence or absence of type 2 diabetes mellitus (T2DM). In the T2DM subgroup, 65 patients received esaxerenone and 55 received an ARB. In the non-T2DM subgroup, 135 and 145 patients received these treatments, respectively. The least squares mean change from baseline at the end of treatment in morning home systolic blood pressure in the T2DM subgroup was −10.9 (95% confidence interval −13.5, −8.4) mmHg in esaxerenone-treated patients and −8.8 (−11.5, −6.0) mmHg in ARB-treated patients; in the non-T2DM subgroup, these were −10.5 (−12.3, −8.7) mmHg and −9.1 (−10.8, −7.3) mmHg, respectively. Although this subgroup analysis was not powered to formally demonstrate non-inferiority, the between-treatment differences in morning home SBP were consistent with the non-inferiority of esaxerenone to ARBs based on the margin used in the primary analysis in both the T2DM and non-T2DM subgroups. Urinary albumin-to-creatinine ratio (UACR) significantly decreased in esaxerenone-treated patients with T2DM (−33.4%), but not in those without T2DM. In contrast, UACR significantly decreased in ARB-treated patients without T2DM (−21.2%), but not in those with T2DM. One esaxerenone-treated patient in the non-T2DM subgroup had a serum potassium level ≥6.0 mEq/L, and a low proportion of esaxerenone-treated patients in the non-T2DM subgroup had hypokalemia (2.2%). Overall, this subgroup analysis showed favorable antihypertensive and kidney-protective effects (based on UACR) of esaxerenone, combined with an acceptable safety profile, in patients with hypertension. Moreover, antihypertensive effects were observed regardless of T2DM status, supporting the use of esaxerenone in older patients with hypertension and comorbid T2DM.