Spironolactone does not reduce heart-related death or hospitalization in patients on dialysis

Researchers report that spironolactone, a medication for high blood pressure and heart failure, does not reduce the risk of heart-related death or hospitalization among patients with kidney failure who are receiving dialysis. Earlier studies had suggested that there might be such a benefit to these patients.

The findings were published on August 14 in The Lancet and presented at the European Renal Association / ERA Congress 2025.

“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,” said Michael Walsh MD, PhD, principal investigator of the study and senior scientist at the Population Health Research Institute (PHRI), a joint institute of McMaster University and Hamilton Health Sciences in Hamilton, Ontario, Canada.

As background, the authors noted that patients receiving dialysis are at substantial risk of cardiovascular morbidity and mortality. “We aimed to establish if spironolactone reduces heart failure and cardiovascular deaths in these patients,” they said.

The ACHIEVE trial was a randomized study undertaken internationally in 143 dialysis programs.

The subjects were 45 years or older, or aged 18 years or older with a history of diabetes. All had received dialysis for kidney failure for at least 3 months at the time of recruitment.

Subjects who could tolerate and adhere to spironolactone 25 mg daily orally during a run-in phase to the trial were randomly assigned to continue spironolactone or receive a matching placebo.

The primary outcome was a composite of cardiovascular mortality or hospitalization for heart failure.

The investigators enrolled 3565 subjects in the open-label run-in phase, and 2538 were subsequently randomized to spironolactone (n=1260) or placebo (n=1278). Of the total study population, 931 (36·7%) were female and 1607 (63·3%) were male.

Median follow-up was 1.8 years.

After an interim analysis of 75% of the expected primary outcome events, the external safety and efficacy monitoring committee recommended that the trial be stopped early for futility.

At the time the trial was stopped, the composite primary outcome of heart failure and cardiovascular death had occurred in 258 subjects in the spironolactone group and in 276 subjects in the placebo group, a statistically non-significant difference (p=0·35).

Death from any cause was similar in both groups as was hospitalization for any cause.

The authors concluded, “Among patients receiving maintenance dialysis, spironolactone 25 mg daily orally did not reduce the composite outcome of cardiovascular mortality and hospitalisation due to heart failure compared with placebo. This trial did not identify a benefit of initiating spironolactone in patients receiving maintenance dialysis. Future research should consider alternatives to steroidal mineralocorticoid receptor antagonism to reduce cardiovascular morbidity and mortality in patients receiving maintenance haemodialysis.”