Spironolactone Misses Mark in Hemodialysis Trial

Patrick Rossignol, MD, PhD

Credit: Boehringer Ingelheim

Primary results from the phase 3b ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial (ALCHEMIST) trial provide an overview of the impact of spironolactone treatment in chronic hemodialysis patients with cardiovascular complications.

Presented at the American Society of Nephrology Kidney Week 2023 by Patrick Rossignol, MD, PhD, head of medical specialties service at Princess Grace Hospital and medical director at Monaco Private Haemodialysis Centre, results showed spironolactone missed its primary endpoint and failed to significantly reduce the incidence of most outcomes, with hospitalization for heart failure serving as the lone exception.¹

“Of all the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group. Secondary analyses will help us understand this finding,” said Rossignol.

A potassium-sparing diuretic, spironolactone prevents the overabsorption of salt and helps patients maintain healthy potassium levels. It can be used in combination with other medicines to treat high blood pressure, heart failure, edema, and hyperaldosteronism, all of which are complications of hemodialysis. Cardiovascular disease underlies the majority of deaths in patients with dialysis-dependent end-stage renal disease, but little is known about the use of standard cardiovascular therapies in this patient population.^2,3

To assess the impact of treatment with spironolactone on clinical outcomes in hemodialysis patients, investigators recruited patients with end-stage renal disease on hemodialysis with at least 1 comorbidity, cardiovascular abnormality, or cardiovascular risk factor from 64 sites in France, Belgium, and Monaco. Investigators included 794 patients in the run-in period and administered spironolactone at a 25 mg dose every 2 days in practice after the hemodialysis session, 3 times per week.¹

Patients were then randomly assigned to receive spironolactone or placebo titrated to a maximum single dose of 25 mg per day over 1 month. However, patients from the run-in period were excluded from randomization if their serum potassium exceeded 5.5 mmol/l. In total, 644 participants were included in the intention-to-treat population and randomized to receive spironolactone (n = 320) or placebo (n = 324).¹

The primary outcome of interest was time to onset of nonfatal myocardial infarction, acute coronary syndrome, hospitalization for heart failure, nonfatal stroke, or cardiovascular-induced death. Investigators noted among 644 randomized patients with a median follow-up of 32.6 (interquartile range, 17.3-48.4) months, 396 withdrew for the following reasons:

• 247 (62.4%) death
• 55 (13.9%) wish to stop
• 31 (7.8%) renal transplant
• 30 (7.6%) medical decision
• 1 (0.3%) protocol violation
• 32 (8.1%) other

Among participants assigned to spironolactone, 123 completed the study and 197 withdrew. Among participants assigned to placebo, 125 completed the study and 199 withdrew.¹

Upon analysis, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome compared to placebo (hazard ratio [HR], 0.996; confidence interval [CI], 0.729-1.362; P = .9819). An additional analysis of the individual components of the primary outcome revealed the incidence of hospitalization for heart failure was statistically significantly lower in the spironolactone group (HR, 0.412; CI, 0.171-0.995; P = .0487).¹

References:

1. Rossignol P, Zannad F Massy ZA, et al. ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial (ALCHEMIST): Primary Results. Paper Presented at: American Society of Nephrology Kidney Week 2023. November 1-5, 2023.
2. Mayo Clinic. Hemodialysis. Tests & Procedures. August 5, 2023. Accessed November 3, 2023. https://www.mayoclinic.org/tests-procedures/hemodialysis/about/pac-20384824
3. Mayo Clinic. Spironolactone (Oral Route). Drugs and Supplements. October 1, 2023. Accessed November 3, 2023. https://www.mayoclinic.org/drugs-supplements/spironolactone-oral-route/description/drg-20071534