Effect of Body Mass Index on the Efficacy and Safety of Esaxerenone Versus Trichlormethiazide for the Treatment of Japanese Patients with Uncontrolled Essential Hypertension: A Subanalysis of the Excite-HT Study.

This prespecified, exploratory, body mass index (BMI)-stratified analysis of the randomized, open-label EXCITE-HT study examined whether esaxerenone elicits a blood pressure (BP)-lowering effect similar to trichlormethiazide in Japanese patients with uncontrolled essential hypertension. Patients received either esaxerenone or trichlormethiazide for 12 weeks and were grouped by baseline BMI: <25 kg/m² (low) or ≥25 kg/m² (high). The primary endpoint was change in morning home systolic/diastolic BP (SBP/DBP). Among 585 patients, 157 and 135 with low BMI received esaxerenone and trichlormethiazide, respectively; in the high BMI subgroup, 138 and 155 patients received esaxerenone or trichlormethiazide. The least squares mean between-group differences (esaxerenone-trichlormethiazide) were -2.1 mmHg (95% confidence interval [-4.1, -0.1])/-0.1 mmHg (-1.2, 1.0) and -2.0 mmHg (-4.0, -0.1)/-1.0 mmHg (-2.2, 0.2) for SBP/DBP in the low and high BMI subgroups, respectively. Bedtime home and office BP showed comparable tendencies. The incidence of serum potassium <3.5 mEq/L was more common with trichlormethiazide, whereas serum potassium ≥5.5 mEq/L occurred more frequently with esaxerenone; serum potassium never reached ≥6.0 mEq/L in any subgroup. Both drugs showed transient, modest decreases in creatinine-based estimated glomerular filtration rate that stabilized by Week 12. These exploratory findings, consistent with the primary study results, suggest that esaxerenone provides effective and well-tolerated BP control regardless of baseline BMI and may lower early-morning SBP to a greater extent than trichlormethiazide.

© 2026 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.