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

ABSTRACT

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/m ² (low) or ≥25 kg/m ² (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.