Yonsei University College of Medicine-led research has shown amiloride is as effective as spironolactone in reducing systolic blood pressure (SBP) over 12 weeks in patients with resistant hypertension.

Resistant hypertension affects approximately 10% of hypertensive patients and is associated with worse outcomes than nonresistant cases.

Spironolactone is a fourth-line medication, introduced only after renin-angiotensin system inhibitors, calcium channel blockers, and thiazide diuretics fail to control blood pressure. Adverse effects, particularly hyperkalaemia and hormonal disruptions, limit its use in long-term care. Amiloride, a potassium-sparing diuretic, lacks these hormonal side effects, making it a potential replacement candidate.

In the study, "Spironolactone vs amiloride for resistant hypertension: a randomised clinical trial," published in JAMA, researchers conducted a prospective, open-label, blinded end-point trial to assess whether amiloride could provide comparable SBP reduction to spironolactone in patients with resistant hypertension.

Researchers enrolled 118 participants at 14 hospitals across South Korea. Participants ranged in age from 19 to 75 years and had sustained hypertension despite a four-week run-in period on a fixed-dose triple combination of a renin-angiotensin system inhibitor, calcium channel blocker, and thiazide diuretic.

Participants were randomised 1:1 to receive either 12.5 mg/d of spironolactone or 5 mg/d of amiloride. Dose escalation was permitted after four weeks for those with home SBP at or above 130 mm Hg, increasing to 25 mg/d for spironolactone and 10 mg/d for amiloride. Home BP measurements were recorded twice daily, and adherence was monitored through pill counts.

At 12 weeks, mean home SBP decreased by 13.6 mm Hg in the amiloride group and 14.7 mm Hg in the spironolactone group, a noninferior difference within the trial's prespecified margin (−4.4 mm Hg). Target home SBP below 130 mm Hg was achieved by 66.1% of patients receiving amiloride and 55.2% receiving spironolactone. One case of hyperkalaemia-related discontinuation occurred in the amiloride group; no gynecomastia cases were reported in either group.

Researchers concluded that amiloride demonstrated noninferior efficacy in reducing SBP compared to spironolactone in patients with resistant hypertension, suggesting its potential as an alternative for those intolerant to the adverse effects of spironolactone.

Findings indicate that amiloride may provide an effective treatment option without the hormonal side effects associated with spironolactone, potentially expanding therapeutic strategies for resistant hypertension management.