Understanding ALCHEMIST Results, with Patrick Rossignol, MD, PhD

To the disappointment of many in the community, results of the ALCHEMIST trial indicate use spironolactone did not impact risk of negative cardiovascular outcomes in patients with chronic kidney disease on hemodialysis.

Presented at the American Society of Nephrology Kidney Week 2023, results indicate use was not associated with a reduction in the trial’s primary composite endpoint but pointed to a potential reduction in risk of heart failure hospitalization, which was an individual component of the composite endpoint.¹

With approval dating back to 1960, spironolactone has become a staple in the management of heart failure and for the management of blood pressure. As a result, a greater understanding of its safety and efficacy in comorbid conditions, such as chronic kidney disease, could stand to have a significant impact on care.²

A 644-person trial comparing spironolactone or placebo titrated to a maximum single dose of 25 mg per day over 1 month, the primary composite endpoint of ALCHEMIST included was time to onset of nonfatal myocardial infarction, acute coronary syndrome, hospitalization for heart failure, nonfatal stroke, or cardiovascular mortality.

Results of the study indicated use of 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). Analysis of 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).

For further insight into the trial, the editorial team of HCPLive Nephrology sat down with principal Patrick Rossignol, MD, PhD, head of medical specialties service at Princess Grace Hospital and medical director at Monaco Private Haemodialysis Centre, at Kidney Week 2023.

Disclosures of note for Rossignol include AstraZeneca, Bayer, Novartis, Boehringer Ingelheim, and others.

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. Pfizer. ALDACTONE® (spironolactone). U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/012151s079lbl.pdf