Article Impact Level: HIGH Data Quality: STRONG Summary of JAMA. https://doi.org/10.1001/jama.2025.5129 Dr. Chan Joo Lee et al.
Points
- This clinical trial compared amiloride and spironolactone in patients with resistant hypertension and found similar reductions in systolic blood pressure after 12 weeks of treatment.
- Among 118 participants, amiloride reduced SBP by 13.6 mm Hg compared to 14.7 mm Hg with spironolactone, with a non-significant between-group difference of −0.68 mm Hg.
- A higher percentage of patients in the amiloride group reached the target home SBP below 130 mm Hg compared to those on spironolactone, suggesting effective blood pressure control.
- Adverse effects were minimal, with one hyperkalemia-related discontinuation in the amiloride group and no gynecomastia reported throughout the study.
- The results support amiloride as a non-inferior and well-tolerated alternative to spironolactone for patients managing resistant hypertension, especially those sensitive to hormonal side effects.
Summary
This randomized clinical trial assessed whether amiloride, a potassium-sparing diuretic, is non-inferior to spironolactone in reducing systolic blood pressure (SBP) in patients with resistant hypertension. Conducted at 14 sites across South Korea, the study enrolled 118 participants who had elevated SBP despite a 4-week run-in period on a triple-drug regimen, including angiotensin receptor blockers, calcium channel blockers, and thiazides. Participants were randomly assigned to receive either 12.5 mg/day of spironolactone or 5 mg/day of amiloride, with dose escalation permitted after 4 weeks for patients with a home SBP ≥130 mm Hg.
At 12 weeks, the mean reduction in home-measured SBP was 13.6 mm Hg (SD, 8.6) in the amiloride group and 14.7 mm Hg (SD, 11.0) in the spironolactone group, with no significant between-group difference (−0.68 mm Hg; 90% CI, −3.50 to 2.14 mm Hg). Achieving a target home SBP <130 mm Hg was more common in the amiloride group (66.1%) compared to the spironolactone group (55.2%). The occurrence of hyperkalemia-related discontinuation was low, with one case in the amiloride group, and no cases of gynecomastia were reported in either group.
The findings suggest that amiloride is non-inferior to spironolactone in reducing SBP in patients with resistant hypertension. Amiloride’s lack of hormonal side effects, such as gynecomastia, makes it a potential alternative to spironolactone for patients who are intolerant to these adverse effects. This study highlights amiloride as an effective treatment option, providing an essential alternative for managing resistant hypertension, particularly in those who cannot tolerate spironolactone’s side effects.
Link to the article: https://jamanetwork.com/journals/jama/article-abstract/2834040
References Lee, C. J., Ihm, S.-H., Shin, D.-H., Jeong, J.-O., Kim, J. H., Chun, K.-H., Ryu, J., Lee, H.-Y., Choi, S., Lee, E. M., Choi, J. H., Kim, K.-I., Shin, J., Pyun, W. B., Kim, D.-H., Park, S., & Williams, B. (2025). Spironolactone vs amiloride for resistant hypertension: A randomized clinical trial. JAMA. https://doi.org/10.1001/jama.2025.5129
