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

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.