Amiloride is noninferior to spironolactone in lowering home-measured systolic blood pressure (SBP) among patients with resistant hypertension, according to results from a clinical trial published May 14 in JAMA.

Chan Joo Lee, MD, et al., conducted a prospective, open-label, blinded endpoint randomized trial at 14 sites in South Korea from 2020 to 2024. Eligible patients had home SBP levels ≥130 mm Hg despite four weeks of fixed-dose triple therapy with an ARB, calcium channel blocker and thiazide.

The investigators randomly assigned 118 patients with resistant hypertension (median age 55 years, 30% women) to 12.5 mg/d of spironolactone (n=60) or 5 mg/d of amiloride (n=58). After four weeks, dosages were increased to 25 mg/d and 10 mg/d, respectively, if home SBP remained ≥130 mm Hg and serum potassium was <5.0 mmol/L.

At baseline, the mean SBP was 141.5 mm Hg in the amiloride and 142.3 mm Hg for spironolactone groups, and the groups were similar except that 9% of the amiloride group used alpha blockers while none was used in the spironolactone group.

Results showed that at 12 weeks the reduction in home SBP was 13.6 mm Hg and 14.7 mm Hg in the amiloride and spironolactone groups, for a between-group difference in change of –0.68 mm Hg and meeting the noninferiority criteria for amiloride.

Findings also demonstrated that achievement of SBP <130 mm Hg was equally likely in both the amiloride and spironolactone groups using both home measurements (66.1% vs. 55.2%) and office measurements (57.1% vs. 60.3%). 

Safety events were rare, with only one case of hyperkalemia-related discontinuation in the amiloride group and no cases of gynecomastia in either group.

In an accompanying editorial comment, Robert D. Brook, MD, et al., write that "although spironolactone should remain the first-line agent for most patients with resistant hypertension," they note that if spironolactone is not tolerated, amiloride can now be considered the next best evidence-based option." Additionally, "one could also consider carefully adding amiloride to low-dose spironolactone if required for BP control or to avoid adverse effects seen at higher doses."