Amiloride was found to be as effective as spironolactone in lowering systolic blood pressure in patients with resistant hypertension. It also showed a favorable safety profile, making it a viable alternative with fewer side effects.

A study published in JAMA found that amiloride, a potassium-sparing diuretic, is noninferior to spironolactone in lowering systolic blood pressure in patients with resistant hypertension, offering a potentially safer alternative with fewer side effects.

The randomized clinical trial was conducted at 14 sites across South Korea between November 2020 and February 2024. It included 118 patients with true resistant hypertension, defined as a systolic BP ≥130 mm Hg despite triple-drug therapy. Participants received either spironolactone (12.5–25 mg daily) or amiloride (5–10 mg daily), with doses adjusted based on BP response and serum potassium levels.

After 12 weeks, mean home systolic BP fell by 13.6 mm Hg in the amiloride group and by 14.7 mm Hg in the spironolactone group, with no significant difference between them, confirming amiloride's noninferiority. Both drugs had similar success rates in helping patients achieve target systolic BP (<130 mm Hg).

Notably, amiloride maintained effectiveness regardless of renin or aldosterone levels, while spironolactone's effect was diminished in certain hormonal profiles. Safety outcomes favored amiloride, with fewer adverse effects—only one patient discontinued due to hyperkalemia, and no gynecomastia was reported in either group.

(Source:https://www.medscape.com/viewarticle/amiloride-noninferior-spironolactone-resistant-hypertension-2025a1000c2s )