Amiloride Is Noninferior to Spironolactone for Resistant Hypertension

Is amiloride noninferior to spironolactone for the treatment of resistant hypertension in adults?

The study found amiloride to be noninferior to spironolactone for lowering blood pressure in adults with resistant hypertension. Amiloride is less likely to cause hyperkalemia, gynecomastia, menstrual irregularities, and other androgenic adverse effects. (Level of Evidence = 1b)

Although spironolactone is recommended for the treatment of resistant hypertension, hyperkalemia and androgenic adverse effects often limit tolerability. The investigators identified adults (n = 118), aged 19 to 74 years, who met standard diagnostic criteria for resistant hypertension. Eligible patients randomly received open-label spironolactone (12.5 mg daily) or amiloride (5 mg daily). Dose adjustments to 25 mg daily and 10 mg daily, respectively, occurred based on mean home systolic blood pressure (treatment target was less than 130 mm Hg) and serum potassium levels. Complete follow-up occurred in 97% of participants at 12 weeks.

Using intention-to-treat analysis at 12 weeks, mean home systolic blood pressure decreased similarly in both groups (−13.6 and −14.7 mm Hg, respectively; difference was nonsignificant). Similarly, no significant difference occurred in the rate of achieving the target systolic blood pressure of less than 130 mm Hg.

Study design: Randomized controlled trial (single-blinded)

Funding source: Government and foundation

Allocation: Concealed

Setting: Outpatient (any)

Reference: Lee CJ, Ihm SH, Shin DH, et al. Spironolactone vs amiloride for resistant hypertension: a randomized clinical trial. JAMA. 2025;333(23):2073-2082.