Home blood pressure-lowering effect of a non-steroidal mineralocorticoid receptor blocker, esaxerenone, versus trichlormethiazide for uncontrolled hypertension: the EXCITE-HT randomized controlled study

Abstract

The EXCITE-HT study aimed to evaluate the efficacy and safety of esaxerenone versus thiazide diuretics (trichlormethiazide) as second-line treatment for Japanese patients with uncontrolled essential hypertension. This was a 12-week, multicenter, randomized, open-label, parallel-group study. The non-inferiority of esaxerenone to trichlormethiazide was confirmed if the upper limit of the two-sided 95% confidence interval (CI) for the difference in systolic blood pressure (SBP)/diastolic blood pressure (DBP) change between groups was below 3.9/2.1 mmHg. A total of 295 and 290 patients were included in the esaxerenone and trichlormethiazide groups, respectively. The non-inferiority of esaxerenone to trichlormethiazide was demonstrated: least squares mean change differences in morning home SBP/DBP at end of treatment (EOT) were -2.2 (95% CI, -3.6, -0.8) mmHg for SBP/-0.6 (-1.4, 0.2) mmHg for DBP. Morning home, bedtime home, and office BP significantly decreased (all p < 0.001) from baseline to EOT in both groups. The urinary albumin-to-creatinine ratio and N-terminal pro-brain natriuretic peptide level decreased from baseline to Week 12 in both groups, with no notable intergroup difference. Serum potassium elevations occurred more frequently with esaxerenone, while serum potassium reductions occurred more with trichlormethiazide. Uric acid elevations were observed in both groups, but more frequently with trichlormethiazide than esaxerenone. No cases of gout occurred in this study. Reductions in estimated glomerular filtration rate were similarly observed in both groups. EXCITE-HT is the first randomized controlled study to demonstrate evidence that esaxerenone is non-inferior to trichlormethiazide as second-line treatment for Japanese patients with uncontrolled essential hypertension, with no new safety concerns. The EXCITE-HT study demonstrated the non-inferiority of esaxerenone to trichlormethiazide in its morning home blood pressure lowering effect and safety profile in Japanese patients with uncontrolled essential hypertension who were previously treated with an angiotensin II receptor blocker or calcium channel blocker.

Keywords: Blood pressure; Esaxerenone; Essential hypertension; Japan; Trichlormethiazide.

The EXCITE-HT study demonstrated the non-inferiority of esaxerenone to trichlormethiazide in its morning home blood pressure lowering effect and safety profile in Japanese patients with uncontrolled essential hypertension who were previously treated with an angiotensin II receptor blocker or calcium channel blocker.

Fig. 1

Changes from baseline to EOT in (A–C) morning home, (D) bedtime home, and (E) office BP (full analysis set). For panel B, the red dotted line (3.9 mmHg) and blue dotted line (2.1 mmHg) indicate the non-inferiority criteria. Data are LS mean (95% CI) for panels A and B. Data are arithmetic mean ± standard deviation for panel C. Data are arithmetic mean (95% CI) for panels D and E. *p < 0.001 versus baseline, paired t-test. BP blood pressure, CI confidence interval; DBP diastolic blood pressure, EOT end of treatment, LS least squares; SBP systolic blood pressure

Fig. 2

Percentage change in geometric mean of UACR (A) and change in NT-proBNP (B) during the study period (full analysis set). Data are mean (95% CI) for UACR and mean ± SD for NT-proBNP. *p < 0.001, ^†p < 0.05 versus baseline, paired t-test. CI confidence interval, NT-proBNP N-terminal pro-brain natriuretic peptide, SD standard deviation, UACR urinary albumin-to-creatinine ratio

Fig. 3

Time course changes in eGFRcreat (A), serum K levels (B), and UA (C) during the study period (safety analysis set). Data are mean ± standard deviation. eGFRcreat creatinine-based estimated glomerular filtration rate, K potassium, SD standard deviation, UA uric acid