JAMA

Amiloride noninferior to spironolactone in resistant hypertension

May 16, 2025

Study details: This randomized trial, conducted at 14 sites in South Korea, enrolled 118 patients with resistant hypertension, defined as home systolic blood pressure (SBP) ≥130 mm Hg despite a fixed-dose triple medication regimen. Participants (mean age, 55 years; 70% male) were randomized to receive either spironolactone (12.5-25 mg/day) or amiloride (5-10 mg/day) for 12 weeks.

Results: Mean baseline home SBPs were 141.5 mm Hg and 142.3 mm Hg in the amiloride and spironolactone groups, respectively. At week 12, the mean reduction in home SBP was -13.6 mm Hg in the amiloride group and -14.7 mm Hg in the spironolactone group, with a between-group difference of -0.68 mm Hg (90% confidence interval, -3.50 to 2.14 mm Hg), demonstrating noninferiority of amiloride. Achievement rates of home-measured SBP <130 mm Hg were 66.1% for amiloride and 55.2% for spironolactone, with no significant differences in office-measured SBP achievement rates. One case of hyperkalemia-related discontinuation occurred in the amiloride group, with no cases of gynecomastia reported in either group.

Clinical impact: If spironolactone isn’t tolerated, consider amiloride as the next best evidence-based option in clinical practice for managing resistant hypertension. Also consider carefully adding amiloride to low-dose spironolactone if required for BP control or to avoid adverse effects seen at higher doses.

Source:

Lee CJ, et al. (2025, May 14). JAMA. Spironolactone vs Amiloride for Resistant Hypertension: A Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/40366680/