Study Reveals Spironolactone Ineffective for Cardiovascular Risk in Dialysis Patients

A comprehensive international study has concluded that spironolactone, a medication commonly used to treat high blood pressure and heart failure, does not reduce the risk of cardiovascular-related deaths or hospitalizations in dialysis patients. This finding contradicts earlier studies that suggested potential benefits for this demographic.

The research, published in The Lancet and presented at the ERA Congress 2025, involved 2,538 participants from 143 dialysis centers across 12 countries, making it the largest trial of its kind focused on spironolactone for individuals undergoing dialysis. All participants had been on dialysis for a minimum of three months and were either over 45 years old or over 18 with diabetes.

Principal investigator Michael Walsh emphasized the disparity in treatment responses between dialysis patients and those with normal kidney function, noting that while spironolactone has been effective in reducing cardiovascular events in the general population, its efficacy may not extend to those receiving dialysis.

The study aimed to evaluate whether a low daily dose of spironolactone (25 mg) could inhibit aldosterone, a hormone linked to heart remodeling and increased cardiovascular risk. Researchers were hopeful that the medication could lower rates of cardiovascular deaths or hospitalizations for heart failure in this patient group.

Despite the initial optimism, the results showed no cardiovascular benefits from the drug. Instead, it was associated with a higher likelihood of severe hyperkalemia, a condition characterized by elevated potassium levels that can lead to serious heart complications.

Prior studies had hinted at the possibility of spironolactone being beneficial for dialysis patients; however, those studies were limited in scope and duration. In contrast, the ACHIEVE study was meticulously designed and executed, beginning recruitment in 2018 and concluding in December 2024. Out of 3,565 patients initially recruited, 2,538 who tolerated the drug during a preliminary run-in period were randomly assigned to either receive spironolactone or a placebo. The trial was halted early due to an independent monitoring committee's assessment that a meaningful benefit was unlikely.

The occurrence of cardiovascular deaths or hospitalizations for heart failure was recorded for 258 patients in the spironolactone group compared to 276 in the placebo group, a difference that was not statistically significant. Notably, a gender-based analysis indicated potential variations in outcomes: 163 men receiving spironolactone experienced cardiovascular events compared to 201 in the placebo group, while 95 women in the spironolactone group faced such events versus 75 in the placebo group.

Furthermore, severe hyperkalemia was more prevalent in the spironolactone group, affecting 6.6% of patients compared to 4.5% in the placebo group. Walsh expressed concern regarding the safety of spironolactone in this vulnerable population, highlighting the implications for patient care.

Globally, approximately 2.5 million individuals undergo dialysis for kidney failure, with heart disease being the leading cause of mortality in this group, accounting for roughly 40% of all deaths. Walsh conveyed disappointment over the study's findings but acknowledged the clarity it provides, emphasizing the importance of continued efforts to identify safe and effective treatments for dialysis patients.