Lee Chan Joo, Ihm Sang-Hyun, Shin Dong-Ho, Jeong Jin-Ok, Kim Ju Han, Chun Kyeong-Hyeon, Ryu JiWung, Lee Hae-Young, Choi Seonghoon, Lee Eun Mi, Choi Jung Hyun, Kim Kwang-Il, Shin Jinho, Pyun Wook Bum, Kim Dae-Hee, Park Sungha, Williams Bryan
Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Division of Cardiology, Department of Internal Medicine, Bucheon St Mary's Hospital and the Catholic Research Institute for Intractable Cardiovascular Disease, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea.
JAMA. 2025 May 14. doi: 10.1001/jama.2025.5129.
Amiloride has been proposed as an alternative to spironolactone for treating resistant hypertension. However, no randomized clinical trials have compared the efficacy of spironolactone and amiloride in patients with resistant hypertension.
To determine whether amiloride is noninferior to spironolactone in reducing home-measured systolic blood pressure (SBP) in patients with resistant hypertension.
DESIGN, SETTING, AND PARTICIPANTS: Prospective, open-label, blinded end-point randomized clinical trial conducted at 14 sites in South Korea. From November 16, 2020, to February 29, 2024, 118 patients with home SBP of 130 mm Hg or greater after a 4-week run-in period with a fixed-dose triple medication combination (angiotensin receptor blocker, calcium channel blocker, and thiazide) were enrolled.
Patients were randomized in a 1:1 ratio to receive 12.5 mg/d of spironolactone (n = 60) or 5 mg/d of amiloride (n = 58). If home SBP remained 130 mm Hg or greater and serum potassium was less than 5.0 mmol/L after 4 weeks, dosages were increased to 25 mg/d and 10 mg/d, respectively.
The primary end point was the between-group difference in home SBP change at week 12, with a noninferiority margin of -4.4 mm Hg for the lower bound of the confidence interval. Secondary end points included achievement rates of home- and office-measured SBP of less than 130 mm Hg.
The median age of the study population was 55 years, with 70% male. There were no differences between groups in demographic characteristics other than use of α-blockers (8.6% in the amiloride group and 0% in the spironolactone group). The mean baseline home SBPs were 141.5 (SD, 7.9) mm Hg and 142.3 (SD, 8.5) mm Hg in the amiloride and spironolactone groups, respectively. At week 12, mean home SBP measurements were changed from baseline by -13.6 (SD, 8.6) mm Hg and -14.7 (SD, 11.0) mm Hg in the amiloride and spironolactone groups, respectively (between-group difference in change, -0.68 mm Hg; 90% CI, -3.50 to 2.14 mm Hg), with amiloride demonstrating noninferiority to spironolactone. Home-measured achievement rates of SBP less than 130 mm Hg in the amiloride and spironolactone groups were 66.1% and 55.2%, respectively, and office-measured achievement rates of SBP less than 130 mm Hg were 57.1% and 60.3%, respectively, with no difference between the 2 groups. One case of hyperkalemia-related discontinuation occurred in the amiloride group, with no cases of gynecomastia in either group.
Amiloride was noninferior to spironolactone in lowering home SBP, suggesting that it could be an effective alternative for treatment of resistant hypertension.
ClinicalTrials.gov Identifier: NCT04331691.
氨氯吡咪已被提议作为螺内酯治疗顽固性高血压的替代药物。然而，尚无随机临床试验比较螺内酯和氨氯吡咪在顽固性高血压患者中的疗效。
确定氨氯吡咪在降低顽固性高血压患者家庭自测收缩压（SBP）方面是否不劣于螺内酯。
设计、地点和参与者：在韩国14个地点进行的前瞻性、开放标签、终点盲法随机临床试验。从2020年11月16日至2024年2月29日，118例在使用固定剂量三联药物组合（血管紧张素受体阻滞剂、钙通道阻滞剂和噻嗪类）进行4周导入期后家庭自测SBP为130mmHg或更高的患者入组。
患者按1:1比例随机分组，分别接受12.5mg/d的螺内酯（n = 60）或5mg/d的氨氯吡咪（n = 58）。如果4周后家庭自测SBP仍为130mmHg或更高且血清钾低于5.0mmol/L，则剂量分别增加至25mg/d和10mg/d。
主要终点是第12周时两组家庭自测SBP变化的组间差异，置信区间下限的非劣效性界值为-4.4mmHg。次要终点包括家庭自测和诊室测量SBP低于130mmHg的达标率。
研究人群的中位年龄为55岁，70%为男性。除使用α受体阻滞剂外（氨氯吡咪组为8.6%，螺内酯组为0%），两组在人口统计学特征上无差异。氨氯吡咪组和螺内酯组的平均基线家庭自测SBP分别为141.5（标准差，7.9）mmHg和142.3（标准差，8.5）mmHg。在第12周时，氨氯吡咪组和螺内酯组的平均家庭自测SBP较基线分别变化了-13.6（标准差，8.6）mmHg和-14.7（标准差，11.0）mmHg（组间变化差异为-0.68mmHg；90%置信区间为-3.50至2.14mmHg），表明氨氯吡咪不劣于螺内酯。氨氯吡咪组和螺内酯组家庭自测SBP低于130mmHg的达标率分别为66.1%和55.2%，诊室测量SBP低于130mmHg的达标率分别为57.1%和60.3%，两组之间无差异。氨氯吡咪组发生1例与高钾血症相关的停药事件，两组均无男性乳房发育病例。
氨氯吡咪在降低家庭自测SBP方面不劣于螺内酯，表明它可能是治疗顽固性高血压的有效替代药物。
ClinicalTrials.gov标识符：NCT04331691。
