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

Enyu Imai, Yusuke Ebe, Kunio Hirano, Masami Hashimoto, Tomohiro Katsuya, Takahide Miyamoto, Tatsuo Shimosawa, Hirotaka Nagashima, Kazuomi Kario, Naoki Itabashi, Mitsutoshi Kato, Shizuo Kajiyama, Ayumi Tanabe, Kazuaki Uchiyama, Takashi Taguchi, Mitsuru Ohishi, Noriko Nakamura, Hiroyuki Ohbayashi, Hidenori Ishida

Journal: Hypertension research : official journal of the Japanese Society of Hypertension 2024;47(9):2435-2446

PMID: 39039285

Free Full Text on PubMed Central View on PubMed

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.

Address: Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan. [email protected].; Tohno Chuo Clinic, Mizunami, Gifu, Japan.; Hashimoto Kidney Clinic, Fukuyama, Hiroshima, Japan.; Itabashi Diabetes and Dermatology Medical Clinic, Koga, Ibaraki, Japan.; Kato Clinic of Internal Medicine, Katsushika-ku, Tokyo, Japan.; Uchiyama Clinic, Joetsu, Niigata, Japan.; Hirano Clinic, Morioka, Iwate, Japan.; Primula Clinic, Kagoshima, Kagoshima, Japan.; Miyamoto Clinic of Internal Medicine, Matsumoto, Nagano, Japan.; Tokyo Center Clinic, Chuo-ku, Tokyo, Japan.; Kajiyama Clinic, Kyoto, Kyoto, Japan.; Akaicho Clinic, Chiba, Chiba, Japan.; Nakayamadera Imai Clinic, Takarazuka, Hyogo, Japan.; Ebe Clinic, Nagaoka, Niigata, Japan.; Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Kagoshima, Japan.; Katsuya Clinic, Amagasaki, Hyogo, Japan.; Primary Medical Science Department, Medical Affairs Division, Daiichi Sankyo Co., Ltd., Chuo-ku, Tokyo, Japan.; Data Intelligence Department, Daiichi Sankyo Co., Ltd., Shinagawa-ku, Tokyo, Japan.; Department of Clinical Laboratory, School of Medicine, International University of Health and Welfare, Narita, Chiba, Japan.

DOI: 10.1038/s41440-024-01762-z

Link outs

Free resources

Full Text Sources:

https://pmc.ncbi.nlm.nih.gov/articles/pmid/3903928...

Medical:

https://medlineplus.gov/bloodpressuremedicines.htm...

Subscription / membership required

Full Text Sources:

https://doi.org/10.1038/s41440-024-01762-z

MeSH Terms: Humans, Male, Female, Middle Aged, Hypertension, Aged, Trichlormethiazide, Blood Pressure, Antihypertensive Agents, Mineralocorticoid Receptor Antagonists, Sulfones, Treatment Outcome, Blood Pressure Monitoring, Ambulatory, Essential Hypertension, Pyrroles