Trial finds no cardiovascular benefit and higher safety risks with spironolactone in dialysis patients

A large international study has found that spironolactone, a medication for high blood pressure and heart failure, does not reduce the risk of heart-related death or hospitalizations in people with kidney failure receiving dialysis, despite earlier smaller studies suggesting benefit.

The findings were published on August 14 in The Lancet and presented at ERA Congress 2025.

The study enrolled 2,538 participants from 143 dialysis centres across 12 countries, making it the largest trial to date on spironolactone in people receiving dialysis. All participants had been on dialysis for at least three months and were either over 45 years old, or over 18 with diabetes.

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. We launched the ACHIEVE study to determine the safety and effectiveness of spironolactone in people with kidney failure."

Michael Walsh, 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

Researchers tested whether a low daily dose (25 mg) of spironolactone could block aldosterone, a hormone that causes heart remodeling, fibrosis, and raises cardiovascular risk. They wanted to see if this treatment could lower the risk of cardiovascular death or hospitalization for heart failure in patients with kidney failure. "Aldosterone plays a harmful role in heart disease, and its levels tend to be high in dialysis patients," Walsh said. "That's why we thought spironolactone might help."

Instead, the drug showed no cardiovascular benefit, and it increased the risk of severe hyperkalaemia, a rise in blood potassium levels that can lead to irregular heart rhythms or even death in extreme cases. "Earlier studies suggested this type of medication might help people on dialysis, but they were small and had short follow-ups, unlike our large ACHIEVE study."

The trial began recruiting in 2018 and concluded in December 2024. Of the 3,565 patients recruited, 2,538 who tolerated the drug during a seven-week run-in period were randomly assigned to receive either 25 mg of spironolactone daily or a placebo. The trial was stopped early for futility after an independent monitoring committee determined there was little chance of seeing a meaningful benefit.

Cardiovascular death or hospitalization for heart failure occurred in 258 patients in the spironolactone group, compared to 276 in the placebo group. The difference was not statistically significant. The study noted a potential difference in these incidents between men and women, although more research is needed to understand why:

• Men: 163 (spironolactone) vs. 201 (placebo)
• Women: 95 (spironolactone) vs. 75 (placebo)

Severe hyperkalaemia occurred more often in the spironolactone group: 6.6 per cent of patients in the spironolactone group, compared to 4.5 per cent in the placebo group. "This can be a serious safety concern in an already vulnerable group," Walsh added.

Globally, an estimated 2.5 million people receive dialysis for kidney failure. Heart disease is the leading cause of death in this population, responsible for about 40 per cent of all deaths.

"We really hoped that spironolactone could make a difference for people on dialysis," said Walsh. "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."

ACHIEVE was funded by the Canadian Institutes of Health Research, Medical Research Future Fund, Health Research Council, British Heart Foundation, PHRI, St. Joseph's Healthcare Hamilton, Accelerating Clinical Trials Canada, CanSOLVE CKD, and Dalhousie Department of Medicine.