Home blood pressure-lowering effect of esaxerenone vs trichlormethiazide for uncontrolled hypertension: a prespecified subanalysis of the EXCITE-HT randomized controlled study by age subgroup

This predefined subanalysis of the multicenter, randomized, open-label, parallel-group EXCITE-HT study aimed to determine whether the comparative efficacy and safety of esaxerenone and trichlormethiazide differs with age. Patients were divided into two age subgroups (<65 and ≥65 years). The non-inferiority of esaxerenone to trichlormethiazide was assessed based on the upper limit of the two-sided 95% confidence interval (CI) for the difference in systolic/diastolic blood pressure (SBP/DBP) changes. Esaxerenone was considered non-inferior if this value was <3.9/ < 2.1 mmHg; if it was <0 mmHg, esaxerenone was considered superior in its BP-lowering effect. The results showed that the least squares mean changes in morning home SBP/DBP from baseline to the end of treatment (primary endpoint) were -9.5/-5.7 with esaxerenone and -8.2/-4.9 mmHg with trichloromethiazide (between-group difference: -1.3 [95% CI, -3.3, 0.8]/-0.8 [ - 2.1, 0.5] mmHg) in the subgroup aged <65 years. These changes were -14.6/-7.2 and -11.5/-6.7 (-3.0 [-4.9, -1.2]/-0.5 [-1.5, 0.5] mmHg) in the subgroup aged ≥65 years. The incidences of serum potassium level ≥5.5 mEq/L were 2.2% and 1.9% in the esaxerenone-treated subgroups aged <65 and ≥65 years, respectively. In conclusion, esaxerenone achieved the pre-defined non-inferiority margin to trichlormethiazide in its BP-lowering effect regardless of age. In patients aged <65 years, esaxerenone achieved the non-inferiority margin to trichlormethiazide in lowering both SBP and DBP. In patients aged ≥65 years, esaxerenone was superior to trichlormethiazide in lowering SBP and achieved the non-inferiority margin to trichlormethiazide in lowering DBP. The impact of esaxerenone on serum potassium levels did not show a specific age-related effect. A subgroup analysis of the EXCITE-HT study according to age (<65 and ≥65 years) showed that esaxerenone achieved the pre-defined non-inferiority margin to trichlormethiazide in its BP-lowering effect regardless of age. In patients aged ≥65 years, esaxerenone achieved the superiority margin to trichlormethiazide in lowering SBP.