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

• Published in: Hypertension research Vol. 47; no. 9; pp. 2435 - 2446
• Main Authors: Kario, Kazuomi, Ohbayashi, Hiroyuki, Hashimoto, Masami, Itabashi, Naoki, Kato, Mitsutoshi, Uchiyama, Kazuaki, Hirano, Kunio, Nakamura, Noriko, Miyamoto, Takahide, Nagashima, Hirotaka, Kajiyama, Shizuo, Ishida, Hidenori, Imai, Enyu, Ebe, Yusuke, Ohishi, Mitsuru, Katsuya, Tomohiro, Taguchi, Takashi, Tanabe, Ayumi, Shimosawa, Tatsuo
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.09.2024; Springer Nature Singapore
• Subjects: Aged; Antihypertensive Agents - therapeutic use; Blood pressure; Blood Pressure - drug effects; Blood Pressure Monitoring, Ambulatory; Essential Hypertension - drug therapy; Essential Hypertension - physiopathology; Female; Humans; Hypertension; Hypertension - drug therapy; Male; Middle Aged; Mineralocorticoid Receptor Antagonists - therapeutic use; Potassium; Pyrroles; Sulfones - therapeutic use; Treatment Outcome; Trichlormethiazide - therapeutic use; Essential hypertension; Trichlormethiazide; Blood pressure; Esaxerenone; Japan
• ISSN: 0916-9636; 1348-4214; 1348-4214
• DOI: 10.1038/s41440-024-01762-z

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.