VIENNA, June 6, 2025 (APMnews) – Daily treatment with spironolactone does not reduce cardiovascular risk in dialysis patients, according to a new large phase III study presented Friday during the second late-breaking session of the European Renal Association (ERA) Congress, which took place in Vienna.
Efforts are ongoing to find ways to reduce cardiovascular mortality among patients with end-stage kidney disease undergoing dialysis. Initial studies and meta-analyses had suggested that mineralocorticoid receptor antagonists (MRAs) like spironolactone might offer benefits.
However, the large randomized phase III ACHIEVE trial showed the opposite, as reported by Dr. Michael Walsh of McMaster University in Hamilton, Canada. The trial was even terminated early due to futility.
These findings confirm—now with a larger patient population—the negative results previously observed in the phase III ALCHEMIST trial among hemodialysis patients. Meanwhile, spironolactone has also proven ineffective for cardiovascular prevention in patients with chronic kidney disease who had not yet reached end-stage.
The ACHIEVE study enrolled 2,538 adult dialysis patients at cardiovascular risk (aged over 45 and/or diabetic), all of whom had demonstrated good treatment adherence (>80%) and a serum potassium level below 6 mmol/L during a run-in phase on spironolactone. Participants were then randomized to receive either 25 mg/day of spironolactone or a placebo.
The patients had a mean age of 62 and had been on dialysis for a median of two years; the vast majority (84%) were receiving hemodialysis or hemodiafiltration.
The primary endpoint—composite of cardiovascular death and hospitalization for heart failure—showed no significant difference between the two groups.
There were 11.33 events per 100 patient-years in the control group versus 10.46 events per 100 patient-years in the study group.
The lack of benefit from spironolactone was confirmed through multiple sensitivity analyses.
Only the male subgroup appeared to benefit from the treatment, showing a 19% reduction in cardiovascular events.
No secondary endpoints, including cardiovascular death or hospitalization, were improved with treatment. In contrast, the risk of severe hyperkalemia (serum potassium >6.5 mmol/L) was significantly increased by 54%, despite the careful patient selection during the run-in phase.
This lack of cardiovascular benefit from spironolactone in hemodialysis patients was generalized to all mineralocorticoid receptor antagonists by a meta-analysis presented in the same session by Lonnie Pyne, also of McMaster University.
The meta-analysis included 19 studies, notably the ACHIEVE and ALCHEMIST trials. It was described as being of higher quality than previous meta-analyses on the subject. Earlier analyses had suggested a reduction in cardiovascular mortality with MRAs, but they relied on studies with few events and therefore high risk of bias.
While this new meta-analysis also found no benefit for mortality or hospitalization, it confirmed the increased risk of severe hyperkalemia, with an odds ratio (OR, a measure approximating relative risk) of 1.5.
“Cardiovascular mortality risk remains high in this population, and effective treatments are still urgently needed,” concluded Lonnie Pyne.
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