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

Q: What are the key findings of this study?

Esaxerenone reduced morning home systolic blood pressure similarly to ARBs regardless of diabetes status and decreased urinary albumin-to-creatinine ratio by 33.4% in patients with type 2 diabetes.

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Hypertension (n=400). Intervention: Esaxerenone vs. Angiotensin II receptor blocker (ARB). Primary outcome: Change from baseline in morning home systolic blood pressure at end of treatment (T2DM subgroup) (MD -2.2, 95% CI -5.9, 1.6).

Q: What does this research mean for the field?

In older hypertensive patients on amlodipine, esaxerenone provides blood pressure reduction comparable to ARBs regardless of type 2 diabetes status, while significantly reducing urinary albumin excretion in patients with diabetes. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Mitsuru Ohishi; Kazuomi Kario; Hiroyuki Ohbayashi; Hajime Ishii; Mitsutoshi Kato; Minoru Nozaki; Norio Abiru; Toshiki Fukui; Kazushi Nomura; Yasushi Fukushima; Naoki Itabashi; Kazuaki Uchiyama; Masafumi Nishizawa; Yoshiki Hata; Noriko Nakamura; Satoshi Kodono; Kunio Hirano; Tomohiro Katsuya; Tatsuo Shimosawa; Kazuhito Shiosakai; Taketoshi Furugori; Takashi Taguchi; on behalf of the ESCORT-HT investigators

doi:10.1038/s41440-026-02779-2

Key result

Esaxerenone matches ARBs for morning home SBP control and cuts UACR ~33% in diabetes.

MD -2.2
95% CI -5.9, 1.6
n=400

Why the study?

The antihypertensive efficacy, organ-protective effects, and safety profile of esaxerenone compared with ARBs in older hypertensive patients with and without T2DM were not well established.

Does esaxerenone added to amlodipine reduce morning home systolic blood pressure and improve kidney-protective markers compared to ARBs in older hypertensive patients with and without T2DM?

Key Points

To evaluate the antihypertensive efficacy, organ-protective effects, and safety of esaxerenone compared with an angiotensin II receptor blocker in hypertensive patients aged ≥65 years receiving amlodipine, stratified by type 2 diabetes mellitus status.
Predefined subgroup analysis of the ESCORT-HT trial in hypertensive patients aged ≥65 years taking amlodipine, stratified into a T2DM subgroup (esaxerenone: N=65; ARB: N=55) and a non-T2DM subgroup (esaxerenone: N=135; ARB: N=145).
Patients received either esaxerenone (1.25–2.5 mg daily) or an ARB across a 12-week treatment period.
Least squares mean change from baseline at end of treatment in morning home SBP in the T2DM subgroup was −10.9 (95% CI −13.5, −8.4) mmHg with esaxerenone and −8.8 (−11.5, −6.0) mmHg with ARBs; in the non-T2DM subgroup, changes were −10.5 (−12.3, −8.7) mmHg and −9.1 (−10.8, −7.3) mmHg, respectively.
Least squares mean differences between treatments in morning home SBP were −2.2 (95% CI −5.9, 1.6) mmHg in the T2DM subgroup and −1.4 (−3.9, 1.1) mmHg in the non-T2DM subgroup, consistent with the non-inferiority of esaxerenone to ARBs.
Urinary albumin-to-creatinine ratio significantly decreased in esaxerenone-treated patients with T2DM (−33.4% [95% CI −45.9%, −17.9%], P < 0.001) and in ARB-treated patients without T2DM (−21.2% [95% CI −31.4%, −9.4%], P < 0.001).

Study Design

Type

RCT (n=400)

Blinding

Open-label

Randomization

Randomized

Multicenter

Yes

Structured PICO

Does esaxerenone added to amlodipine reduce morning home systolic blood pressure and improve kidney-protective markers compared to ARBs in older hypertensive patients with and without T2DM?

P

Population

400 older adults (aged ≥65 years) with hypertension inadequately controlled by amlodipine, stratified by the presence of type 2 diabetes mellitus, followed for 12 weeks.

I

Intervention

Esaxerenone (starting dose 1.25 or 2.5 mg/day, titrated up to 2.5 mg/day) oral once daily added to continued amlodipine therapy for a 12-week treatment period.

C

Comparator

Angiotensin II receptor blocker (ARB) at standard approved dose (azilsartan, irbesartan, olmesartan, candesartan, telmisartan, valsartan, or losartan) oral once daily added to continued amlodipine therapy for 12 weeks.

O

Outcome

Change from baseline in morning home systolic blood pressure at the end of treatment (12 weeks).surrogate

Main Result

Mean Difference: -2.2 (95% CI -5.9–1.6)

Absolute Event Rate: -10.9% vs -8.8%

Esaxerenone effectively lowers blood pressure and demonstrates significant UACR reduction (kidney-protective effect) in older hypertensive patients with comorbid type 2 diabetes compared to ARBs, with an acceptable safety profile.

Limitations

Subgroup analysis was not specifically powered to formally demonstrate non-inferiority.
No formal treatment-by-T2DM interaction test was performed.
Short study duration of 12 weeks.
Open-label study design may introduce bias.
Subgroup analysis not powered to formally demonstrate non-inferiority
No formal treatment-by-T2DM interaction test was performed
Short 12-week follow-up period
Open-label design

Implication

Supports esaxerenone as ARB alternative for home SBP control in elderly hypertensives with or without T2DM; subgroup data leaves organ-protection role open.

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.

Discussion

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Cite This Study

Ohishi et al. (2026) conducted an RCT in Hypertension (n=400). Esaxerenone vs. Angiotensin II receptor blocker (ARB) was evaluated on Change from baseline in morning home systolic blood pressure at end of treatment (T2DM subgroup) (MD -2.2, 95% CI -5.9, 1.6). Esaxerenone reduced morning home systolic blood pressure similarly to ARBs regardless of diabetes status and decreased urinary albumin-to-creatinine ratio by 33.4% in patients with type 2 diabetes.

synapsesocial.com/papers/6acae65a082e6266f39bf595 https://doi.org/10.1038/s41440-026-02779-2

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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

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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