Large International Study Finds Spironolactone Ineffective in Reducing Cardiovascular Risk in Dialysis Patients

A comprehensive global clinical trial has revealed that spironolactone, a medication commonly used to treat high blood pressure and heart failure, does not decrease the risk of cardiovascular death or hospitalizations among patients undergoing dialysis due to kidney failure. Despite earlier smaller studies hinting at potential benefits, this large-scale research indicates no significant cardiovascular improvements with the use of this drug in this specific population.

The study, published in The Lancet and presented at ERA Congress 2025, enrolled 2,538 participants from 143 dialysis centers across 12 countries, making it the largest trial to date investigating spironolactone’s effects in dialysis patients. Participants had been on dialysis for at least three months and were either over 45 or over 18 with diabetes.

Researchers aimed to assess whether a low dose (25 mg daily) of spironolactone could counteract the effects of aldosterone, a hormone implicated in heart remodeling, fibrosis, and increased cardiovascular risk. The premise was that blocking aldosterone might reduce heart-related deaths and hospital admissions. However, the findings showed no statistically significant difference between those receiving spironolactone and the placebo group regarding cardiovascular outcomes.

Furthermore, the trial observed a concerning rise in severe hyperkalemia — dangerously high blood potassium levels — in the spironolactone group, affecting 6.6% of participants versus 4.5% in the placebo group. This condition can lead to irregular heart rhythms and even sudden death, raising safety concerns about the medication’s use in this vulnerable population.

The trial began recruiting in 2018 and concluded in December 2024, but was halted early due to futility, as the independent monitoring committee determined that continuing treatment was unlikely to demonstrate significant benefits. Results showed similar rates of cardiovascular death or hospitalization: 258 patients in the spironolactone group versus 276 in the placebo group.

Interestingly, there were hints of differences between men and women, with men experiencing fewer adverse events on spironolactone compared to women, though further research is needed to explore this observation.

The study underscores the complexity of treating cardiovascular risks in dialysis patients, a group in which heart disease is the leading cause of death, accounting for about 40% of fatalities. Despite the initial hope that spironolactone might offer a beneficial intervention, the findings emphasize the importance of rigorous, large-scale trials to validate potential therapies.

According to Michael Walsh, the principal investigator, “While we hoped spironolactone would help, our results show it does not reduce cardiovascular risks and poses safety concerns due to hyperkalemia.” He added, “This study helps clarify the limited role of this medication in dialysis patients and highlights the urgent need for effective and safe treatment options.”

For more detailed information, see the full study in The Lancet. Source: https://medicalxpress.com/news/2025-08-global-heart-failure-drug-spironolactone.html