Spironolactone Shows No Cardiovascular Benefit in Dialysis Patients

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Michael Walsh, MD

Credit: Population Health Research Institute

Among patients receiving maintenance dialysis for kidney failure, spironolactone 25 mg daily orally does not reduce cardiovascular mortality and hospitalization due to heart failure compared with placebo, according to findings from the ACHIEVE trial.1

The international, parallel-group, randomized controlled trial was conducted in 143 dialysis programs across 12 countries and was stopped early for futility at the recommendation of the external safety and efficacy monitoring committee after a planned interim analysis of 75% of the expected primary outcome events.1

“In people with normal kidney function, spironolactone reduces cardiovascular events. However, people receiving dialysis might not respond the same way to treatments proven effective in the general population,” Michael Walsh, principal investigator of the study and senior scientist at the Population Health Research Institute at McMaster University and Hamilton Health Sciences, said in a statement.2 “We launched the ACHIEVE study to determine the safety and effectiveness of spironolactone in people with kidney failure.”

Spironolactone, a mineralocorticoid receptor agonist, is commonly used in the management and treatment of hypertension and heart failure. The drug recently made headlines when the US Food and Drug Administration announced a recall of > 11,000 100-count bottles of spironolactone 25 mg tablets due to the presence of a foreign substance later identified as aluminum.3

Cardiovascular disease underlies the majority of deaths in patients with dialysis-dependent end-stage renal disease, necessitating research about the use of standard cardiovascular therapies in this patient population.2

ACHIEVE enrolled patients ≥ 45 years of age, or ≥ 18 years of age with a history of diabetes, who were receiving maintenance dialysis for kidney failure for ≥ 3 months at the time of recruitment. Patients who were able to tolerate and adhere to spironolactone 25 mg daily orally during an open-label run-in were randomly assigned in a 1:1 ratio to continue spironolactone or matching placebo. Participants, health-care providers, and those assessing outcomes were masked to group assignment.1

The primary outcome was a composite of cardiovascular mortality or hospitalization for heart failure analyzed as time-to-event in all randomly assigned participants.1

From September 2017, to October 2024, 3689 patients were screened for inclusion, 3565 of whom were enrolled in the open-label run-in phase, and 2538 were randomly assigned to spironolactone (n = 1260) or placebo (n = 1278). Among the cohort, 931 (36.7%) participants were female and 1607 (63.3%) were male.1

During a median follow-up of 1,8 (interquartile range, 0.85–3.35) years, the composite primary outcome occurred in 258 participants (10.46 events per 100 patient-years) in the spironolactone group and in 276 participants (11.33 per 100 patient-years) in the placebo group (hazard ratio [HR], 0.92; 95% CI, 0.78–1.09; P = .35). Investigators noted death from any cause was similar between groups (HR, 0.95; 95% CI, 0.83–1.09) as was hospitalization for any cause (HR, 0.96; 95% CI, 0.87–1.06).1

“We really hoped that spironolactone could make a difference for people on dialysis,” said Walsh.2 “While the results are not what we wanted, they provide much-needed clarity. This study moves us one step closer to finding effective and safe treatments for a group that urgently needs them.”

References
  1. Walsh M, Collister D, Gallagher M, et al. Spironolactone versus placebo in patients undergoing maintenance dialysis (ACHIEVE): an international, parallel-group, randomised controlled trial. The Lancet. doi:10.1016/S0140-6736(25)01198-5
  2. McMaster University. Global study finds heart failure drug spironolactone fails to lower cardiovascular risk in dialysis patients. EurekAlert! August 14, 2025. Accessed August 15, 2025. https://www.eurekalert.org/news-releases/1094592
  3. Livingston R. FDA, Sun Pharmaceuticals Issue National Recall of Spironolactone 25 mg Tablets. HCPLive. August 12, 2025. Accessed August 15, 2025. https://www.hcplive.com/view/fda-sun-pharmaceuticals-issue-national-recall-of-spironolactone-25-mg-tablets

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