ACHIEVE: Spironolactone Fails to Reduce Cardiovascular Risk in Dialysis Patients

Results from the ACHIEVE trial at 62nd European Renal Association (ERA 2025) Congress indicate use of spironolactone, a mineralocorticoid receptor agonist, did not significantly reduce the risk of cardiovascular death or heart failure hospitalization in patients undergoing maintenance dialysis, despite earlier hypotheses that mineralocorticoid receptor blockade could provide cardioprotective benefits in this high-risk population.

Adding to data from previous trials, such as ALCHEMIST, results of the study suggest the primary composite outcome of cardiovascular death or hospitalization for heart failure occurred in 20.5% of patients in the spironolactone group versus 21.6% in the placebo group (HR, 0.92; 95% CI, 0.78 to 1.09; P = .35).

“So far, very few interventions appear to actually be effective, so there's a lot of hope around any intervention that will actually reduce cardiovascular mortality,” explained lead investigator Michael Walsh, MD, of McMaster University in an interview with HCPLive at ERA 2025. “Aldosterone has been pretty heavily implicated, with a high risk ratio for those who have elevated aldosterone and, in fact, aldosterone is elevated in most dialysis patients. So it seemed like it would be a widespread target to be able to try and treat and in previous small studies, there was a very large signal for risk reduction of cardiovascular mortality, like up to 60% reduction in cardiovascular mortality probably too good to be believed, which is why we felt like we needed to do a large, high quality study.”

The trial included 2532 patients randomized after an open-label run-in phase confirming tolerability of spironolactone 25 mg daily. Participants were assigned to receive either spironolactone or placebo, with a median follow-up designed to assess major cardiovascular outcomes.

Rates of secondary outcomes—including cardiac death, vascular death, all-cause mortality, and all-cause hospitalizations—were also similar between groups. However, severe hyperkalemia occurred more frequently in the spironolactone group (6.6%) compared with placebo (4.5%), representing a 44% increased risk (HR, 1.44; 95% CI, 1.03 to 2.01). Sensitivity analyses, including per-protocol and expanded heart failure hospitalization definitions, produced similar findings.

To hear more on the trial’s outcomes, limitations, and the path forward in cardiovascular risk reduction for dialysis patients, watch our full interview with Walsh from the floor at ERA 2025.

Relevant disclosures for Walsh include Otsuka, GSK, Bayer, Novo Nordic, and Hansa Pharma.

Reference:

Walsh M, Collister D, Gallagher M, et al. Spironolactone in patients undergoing maintenance dialysis: the ACHIEVE trial. Presented at: 62nd European Renal Association Congress. June 04 – 07, 2025. Vienna, Austria.