Key result
Esaxerenone matches ARBs for lowering morning home SBP in older adults.
Why the study?
Age-related differences in the efficacy and safety of esaxerenone compared to angiotensin II receptor blockers in older hypertensive patients were not well characterized.
Does esaxerenone improve blood pressure reduction compared to ARBs in older adults with inadequately controlled hypertension on amlodipine?
RCT (n=402)
Open-label
1:1 using block randomization with BP and age as allocation variables
Yes
Does esaxerenone improve blood pressure reduction compared to ARBs in older adults with inadequately controlled hypertension on amlodipine?
Effect estimate: MD -1.1 mmHg (65-74 years) and MD -2.2 mmHg (≥75 years) (95% CI -3.8, 1.6 (65-74 years); -5.2, 0.9 (≥75 years))
Esaxerenone is a non-inferior alternative to ARBs for reducing blood pressure in older patients on CCBs, while potentially offering cardioprotective benefits as reflected by reduced NT-proBNP.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“From these studies, there will be a promise that esaxerenone could be a second-line antihypertensive agent to choose in various conditions, especially in patients with suspected MR-associated and uncontrolled hypertension.”
“In antihypertensive therapy for the elderly, who are expected to have many salt-sensitive and low renin levels that are poorly responsive to renin-angiotensin-aldosterone system inhibitors (RAS) inhibitors, it is hoped that antihypertensive drugs that can be used as first-line or second-line drugs will have sufficient safety and sufficient antihypertensive effects. However, there are limited clinical studies of antihypertensive drugs targeting elderly Japanese people in this latter life stage, and Kario et al. have made a contribution to answering such clinical questions.”
Supports esaxerenone as a non-inferior ARB alternative for older adults on amlodipine; confirms efficacy in predefined 65–74 and ≥75 subgroups.
The ESCORT-HT study recently demonstrated non-inferiority of esaxerenone to angiotensin II receptor blockers (ARBs) in lowering morning home systolic blood pressure (SBP) in Japanese patients aged ≥65 years with inadequately controlled hypertension on amlodipine. This predefined subgroup analysis of the ESCORT-HT study analyzed age-related differences in the efficacy and safety of esaxerenone relative to ARBs. In the 65–74-year subgroup, 98 patients were treated with esaxerenone and 94 with an ARB; in the ≥75-year subgroup, 104 were treated with esaxerenone and 106 with an ARB. The least squares mean difference in morning home SBP between the two treatment groups at end of treatment was −1.1 (95% confidence interval [CI] −3.8, 1.6) mmHg for the 65–74-year subgroup and −2.2 (95% CI −5.2, 0.9) mmHg for the ≥75-year subgroup. The upper bound of the 95% CI was within the pre-defined non-inferiority margin of <3.8 mmHg. The urine albumin-to-creatinine ratio decreased in all groups at Week 12, regardless of age or treatment, and N-terminal pro-B-type natriuretic peptide levels decreased in esaxerenone-treated patients, regardless of age. The incidence of treatment-emergent adverse events was 34.3% (esaxerenone) and 32.0% (ARB) in patients 65–74 years, and 16.7% and 29.6%, respectively, in patients aged ≥75 years. There were no notable increases in the incidence of hyperkalemia or hypokalemia, relative to ARBs, in any of the age subgroups. This predefined subgroup analysis of the ESCORT-HT study showed antihypertensive effects consistent with the non-inferiority of esaxerenone to ARBs in both age groups, and suggested a potential cardioprotective effect, including for patients aged ≥75 years.
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Kario et al. (2026) conducted an RCT in Hypertension (n=402). Esaxerenone vs. Angiotensin II receptor blockers (ARBs) was evaluated on Change from baseline in morning home SBP at end of treatment (least squares mean difference) (MD -1.1 mmHg (65-74 years) and MD -2.2 mmHg (≥75 years), 95% CI -3.8, 1.6 (65-74 years); -5.2, 0.9 (≥75 years)). Esaxerenone demonstrated non-inferiority to ARBs for reducing morning home systolic blood pressure in both the 65–74 and ≥75 age groups, with upper bounds of 95% CIs within the 3.8 mmHg margin.
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