By Lucy Piper, medwireNews Reporter
medwireNews: The diuretic amiloride may be a suitable treatment alternative to spironolactone for patients with resistant hypertension, suggests a study published in JAMA.
After 12 weeks of treatment, home measurements of systolic blood pressure (SBP) were reduced by an average 13.6 mmHg with amiloride and 14.7 mmHg with spironolactone, from baseline means of 141.5 mmHg and 142.3 mmHg, respectively, the researchers report.
The SBP reduction with amiloride was a nonsignificant 0.68 mmHg smaller than with spironolactone and the lower confidence interval of –3.50 mmHg was within the –4.40 mmHg margin for noninferiority.
“Spironolactone is the drug of choice when BP is not controlled with maximally tolerated doses of renin-angiotensin system inhibitors, calcium channel blockers, and thiazide-like/-type diuretics,” note the researchers.
However, they add that “[u]nlike spironolactone, amiloride does not have antiandrogenic adverse effects and has a lower incidence of hyperkalemia, potentially making it a better option for resistant hypertension treatment if the BP-lowering efficacy is similar.”
To investigate, Sungha Park (Yonsei University College of Medicine, Seoul, South Korea) and colleagues enrolled 164 adults with resistant hypertension from 14 tertiary care hospitals in South Korea to a 4-week run-in phase during which they received a fixed triple medication combination including an angiotensin receptor blocker, calcium channel blocker, and thiazide.
Of these participants, 118 still had a home SBP of 130 mmHg or above at the end and were randomly assigned to receive amiloride or spironolactone for 12 weeks, while continuing stable doses of other antihypertensives, such as β blockers and α blockers as required. They were a mean of 55 years old, and the majority (70%) were men.
The 58 patients in the amiloride group received a daily dose of 5 mg for the first 4 weeks, which was then increased to 10 mg if the patients’ home SBP remained above 130 mmHg and their serum potassium level was below 5.0 mmol/L. The same regimen was used for the 60 patients in the spironolactone group, who started on a daily dose of 12.5 mg and increased to 25.0 mg.
The two groups were well matched at baseline except for a greater use of α blockers in the amiloride than the spironolactone group (8.6 vs 0%).
Park and co-workers note that the “noninferior BP-lowering effect of amiloride compared with spironolactone was consistent regardless of age, sex, and diabetes status.”
They also found that amiloride was comparable to spironolactone in the proportion of patients who achieved a home-measured SBP below 130 mmHg at 12 weeks, at a corresponding 66.1% and 55.2%.
One difference the investigators report was better SBP-lowering with spironolactone in patients who had high baseline plasma renin activity or a high aldosterone to renin ratio, whereas these factors had no effect on SBP-lowering with amiloride.
“Further research on choosing antihypertensive medications based on baseline aldosterone to renin ratio or plasma renin activity may enhance treatment success in resistant hypertension,” they say.
The safety profile and tolerability of both drugs was “excellent,” note the study authors.
Three patients discontinued amiloride (dizziness in two patients and hyperkalemia in one patient) and one patient discontinued spironolactone (dizziness and acute kidney injury). There was only one serious adverse event (AE) of an ankle fracture in the amiloride group and no cases of gynecomastia.
The researchers point out that the low rate of AEs in the spironolactone group “may be a result that could weaken the need for amiloride as a substitute for spironolactone.”
They also acknowledge that as low doses of the drugs were used, it remains to be determined if they have comparable efficacies at higher doses when the risk for AEs may also be greater.
Nevertheless, the authors conclude that the “results support amiloride as a possible alternative to spironolactone as a fourth-line agent in patients with resistant hypertension.”
Whether amiloride should be considered first-line for resistant hypertension, however, was questioned in a related editorial by Robert Brook (Wayne State University, Detroit, Michigan, USA) and co-authors.
They say that due to the lack of difference in AEs between the two drugs and the potential cardiovascular benefits with mineralocorticoid receptor blockers such as spironolactone, it “should remain the first-line agent for most patients with resistant hypertension.”
However, the editorialists conclude that when “spironolactone is not tolerated, amiloride can now be considered the next best evidence-based option.”
News stories are provided by medwireNews, which is an independent medical news service provided by Springer Healthcare Ltd. © 2025 Springer Healthcare Ltd, part of Springer Nature
JAMA 2025; doi:10.1001/jama.2025.5129
https://pubmed.ncbi.nlm.nih.gov/40366680
JAMA 2025; doi:10.1001/jama.2025.4321