韩国延世大学医学院Bryan Williams团队比较了螺内酯和阿米洛利治疗顽固性高血压患者的疗效与安全性。这一研究成果发表在2025年5月14日出版的《美国医学会杂志》上。

阿米洛利已被提议作为螺内酯治疗顽固性高血压的替代品。然而，没有随机临床试验比较螺内酯和阿米洛利在顽固性高血压患者中的疗效。

为了确定在降低顽固性高血压患者家中测量的收缩压（SBP）方面，阿米洛利是否优于螺内酯。研究组进行了一项前瞻性、开放标签、盲法终点随机临床试验，在韩国14个地点进行。从2020年11月16日至2024年2月29日，118例家庭收缩压为130 mm Hg或更高的患者在4周的磨合期后接受了固定剂量的三联用药（血管紧张素受体阻滞剂、钙通道阻滞剂和噻嗪）。

将患者按1:1的比例随机接受12.5 mg/d的螺内酯（n= 60）或5 mg/d的阿米洛利（n= 58）。如果4周后家庭收缩压维持在130 mm Hg或更高，血清钾低于5.0 mmol/L，则剂量分别增加到25 mg/d和10 mg/d。主要终点是第12周家中收缩压变化的组间差异，置信区间下界的非劣效性裕度为- 4.4 mm Hg。次要终点包括家庭和办公室测量的收缩压低于130毫米汞柱的完成率。

研究人群的中位年龄为55岁，其中70%为男性。除了α-受体阻滞剂的使用（阿米洛利组为8.6%，螺内酯组为0%）外，两组间的人口学特征没有差异。阿米洛利组和螺内酯组的平均基线家庭血压分别为141.5 (SD, 7.9) mm Hg和142.3 (SD, 8.5) mm Hg。在第12周，阿米洛利组和螺内酯组的平均家庭收缩压测量值与基线相比分别变化了13.6 (SD, 8.6) mm Hg和14.7 (SD, 11.0) mm Hg（组间变化差异为0.68 mm Hg；90% CI, - 3.50 - 2.14 mm Hg），阿米洛利与螺内酯相比无劣效性。

阿米洛利组和螺内酯组收缩压< 130 mm Hg家庭测量成功率分别为66.1%和55.2%，办公室收缩压< 130 mm Hg测量成功率分别为57.1%和60.3%，两组间差异无统计学意义。阿米洛利组出现一例高钾血症相关停药，两组均无男性乳房发育病例。

研究结果表明，阿米洛利在降低家庭收缩压方面不逊于螺内酯，这表明它可能是治疗顽固性高血压的有效选择。

附：英文原文

Title: Spironolactone vs Amiloride for Resistant Hypertension: A Randomized Clinical Trial

Author: Chan Joo Lee, Sang-Hyun Ihm, Dong-Ho Shin, Jin-Ok Jeong, Ju Han Kim, Kyeong-Hyeon Chun, JiWung Ryu, Hae-Young Lee, Seonghoon Choi, Eun Mi Lee, Jung Hyun Choi, Kwang-Il Kim, Jinho Shin, Wook Bum Pyun, Dae-Hee Kim, Sungha Park, Bryan Williams

Issue&Volume: 2025-05-14

Abstract:

Importance  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.

Objective  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.

Intervention  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.

Main Outcomes and Measures  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.

Results  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.

Conclusions and Relevance  Amiloride was noninferior to spironolactone in lowering home SBP, suggesting that it could be an effective alternative for treatment of resistant hypertension.

DOI: 10.1001/jama.2025.5129

Source: https://jamanetwork.com/journals/jama/fullarticle/2834040