Esaxerenone versus angiotensin II receptor blockers as second-line therapy in older Japanese patients with uncontrolled hypertension on calcium channel blockers: the randomized, open-label ESCORT-HT study

Q: What are the key findings of this study?

Esaxerenone was non-inferior to ARBs in lowering morning home systolic blood pressure (mean difference -1.6 mmHg) in older patients with uncontrolled hypertension on amlodipine.

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Uncontrolled hypertension (n=402). Intervention: Esaxerenone vs. Angiotensin II receptor blockers (ARBs). Primary outcome: Least squares mean change from baseline in morning home systolic blood pressure (SBP) at end of treatment (Mean Difference -1.6, 95% CI -3.7 to 0.5).

Q: What does this research mean for the field?

Esaxerenone is non-inferior to angiotensin II receptor blockers in lowering morning home systolic blood pressure as a second-line therapy in older patients with uncontrolled hypertension on amlodipine. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.SUPPORTS_CONSENSUS.

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; Go Kato; Takashi Taguchi; Mitsuru Ohishi; on behalf of the ELMSTAT-HF Investigators

doi:10.1038/s41440-026-02634-4

Key result

Esaxerenone proves non-inferior to ARBs in lowering morning home SBP in older patients on amlodipine.

Mean Difference -1.6
95% CI -3.7 to 0.5
n=402

Figures

Why the study?

Mineralocorticoid receptor blockers are positioned as second-line antihypertensive agents in Japanese guidelines, but evidence in older patients remains limited.

Does esaxerenone reduce morning home systolic blood pressure in older Japanese patients with uncontrolled hypertension on amlodipine compared to ARBs?

Key Points

To determine whether adding esaxerenone is non-inferior to adding an angiotensin II receptor blocker to amlodipine for reducing morning home systolic blood pressure in older Japanese patients with uncontrolled hypertension.
A 12-week, multicenter, randomized, open-label, parallel-group, non-inferiority trial conducted in Japan (ESCORT-HT; jRCTs031240300).
Enrolled 419 patients aged ≥65 years with morning home SBP ≥135 mmHg despite stable amlodipine therapy, randomly allocated to add-on esaxerenone (n = 202) or ARB (n = 200), with a mean age of 75.5 years in both groups.
Least squares mean change from baseline at end of treatment in morning home SBP was −10.6 (95% CI: −12.0, −9.1) mmHg with esaxerenone and −9.0 (−10.4, −7.5) mmHg with ARBs; the between-group difference of −1.6 (−3.7, 0.5) mmHg met the non-inferiority margin of 3.8 mmHg.
Both treatments lowered the urine albumin-to-creatinine ratio, whereas only esaxerenone significantly reduced N-terminal pro-B-type natriuretic peptide levels.
Treatment-emergent adverse events occurred in 25.1% of esaxerenone and 30.8% of ARB recipients, with serious events in 2 versus 7 patients, including one death in the esaxerenone group and hyperkalemia reported in one esaxerenone-treated patient.

Study Design

Type

RCT (n=402)

Blinding

Open-label

Randomization

1:1 block allocation

Multicenter

Yes

Structured PICO

Does esaxerenone reduce morning home systolic blood pressure in older Japanese patients with uncontrolled hypertension on amlodipine compared to ARBs?

P

Population

402 Japanese patients aged ≥65 years (mean age 75.5, ~54% female) with uncontrolled hypertension (morning home SBP ≥135 mmHg) despite stable amlodipine therapy (2.5 mg or 5 mg for ≥4 weeks). Excluded: secondary hypertension, hyperkalemia (>4.8 mEq/L), or kidney dysfunction (eGFR < 45 mL/min/1.73 m2).

I

Intervention

Esaxerenone (starting dose 1.25 mg/day or 2.5 mg/day, up-titrated to 2.5 mg/day) added to amlodipine for 12 weeks.

C

Comparator

Angiotensin II receptor blocker (ARB) at standard once-daily dose (azilsartan, irbesartan, olmesartan medoxomil, candesartan cilexetil, telmisartan, valsartan, or losartan potassium) added to amlodipine for 12 weeks.

O

Outcome

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

Main Result

Effect estimate: Mean Difference -1.6 (95% CI -3.7 to 0.5)

Absolute Event Rate: -10.6% vs -9%

Limitations

Open-label design may introduce bias in treatment efficacy evaluation and adverse event reporting
Short treatment duration of 12 weeks
Efficacy and safety data by the specific type of ARB were not available
Only one type of CCB (amlodipine) was used at limited starting doses (2.5 mg or 5 mg)
Open-label design potential for bias
Efficacy and safety data by specific type of ARB were not available
Only one type of CCB (amlodipine) was used at limited doses (2.5 or 5 mg)

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

Esaxerenone is non-inferior to ARBs in lowering morning home systolic blood pressure when added to amlodipine in older Japanese patients, supporting its use as an effective second-line antihypertensive.

Abstract

Mineralocorticoid receptor blockers (MRBs) are positioned as second-line antihypertensive agents in the 2025 Japanese Society of Hypertension guidelines, yet evidence in older patients remains limited. This 12-week, multicenter, randomized, open-label, parallel-group, non-inferiority ESCORT-HT study (jRCTs031240300; September 2024–June 2025) compared esaxerenone with angiotensin II receptor blockers (ARBs) as add-on therapy to amlodipine in Japanese patients aged ≥65 years whose morning home systolic blood pressure (SBP) remained ≥135 mmHg despite stable amlodipine. The mean age was 75.5 years in both the esaxerenone ( n = 202; female: 52.5%) and ARB ( n = 200; female: 56.5%) groups. At the end of treatment, the least squares mean change from baseline in morning home SBP (primary endpoint) was −10.6 (95% confidence interval: −12.0, −9.1) mmHg with esaxerenone treatment and −9.0 (−10.4, −7.5) mmHg with ARB treatment; the between-group difference was −1.6 (−3.7, 0.5) mmHg, meeting the pre-defined non-inferiority margin (3.8 mmHg). Both treatments lowered the urine albumin-to-creatinine ratio, whereas only esaxerenone significantly reduced N-terminal pro-B-type natriuretic peptide. Treatment-emergent adverse events occurred in 25.1% and 30.8% of the esaxerenone and ARB groups; serious events were reported in 2 versus 7 patients, including one death (esaxerenone group). Hyperkalemia occurred in one esaxerenone-treated patient and none who received ARBs. No serious adverse event was judged to be drug-related. Esaxerenone was non-inferior to ARBs in lowering morning home SBP and showed a favorable safety profile in older Japanese patients with inadequately controlled hypertension on amlodipine. These data support the clinical use of esaxerenone as an effective second-line treatment option for this population.

Discussion

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Cite This Study

Kario et al. (2026) conducted an RCT in Uncontrolled hypertension (n=402). Esaxerenone vs. Angiotensin II receptor blockers (ARBs) was evaluated on Least squares mean change from baseline in morning home systolic blood pressure (SBP) at end of treatment (Mean Difference -1.6, 95% CI -3.7 to 0.5). Esaxerenone was non-inferior to ARBs in lowering morning home systolic blood pressure (mean difference -1.6 mmHg) in older patients with uncontrolled hypertension on amlodipine.

synapsesocial.com/papers/69edad6b4a46254e215b5107 https://doi.org/10.1038/s41440-026-02634-4

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Esaxerenone versus angiotensin II receptor blockers as second-line therapy in older Japanese patients with uncontrolled hypertension on calcium channel blockers: the randomized, open-label ESCORT-HT study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Esaxerenone versus angiotensin II receptor blockers as second-line therapy in older Japanese patients with uncontrolled hypertension on calcium channel blockers: the randomized, open-label ESCORT-HT study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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