Mineralocorticoid Receptor Antagonists in Patients With Heart Failure and Impaired Renal Function

Shingo Matsumoto; Alasdair D Henderson; Li Shen; Mingming Yang; Karl Swedberg; Muthiah Vaduganathan; Dirk J van Veldhuisen; Scott D Solomon; Bertram Pitt; Faiez Zannad; Pardeep S Jhund; John J V McMurray

doi:10.1016/j.jacc.2024.03.426

Mineralocorticoid Receptor Antagonists in Patients With Heart Failure and Impaired Renal Function

J Am Coll Cardiol. 2024 May 6:S0735-1097(24)06945-6. doi: 10.1016/j.jacc.2024.03.426. Online ahead of print.

Affiliations

¹ British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
² Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
³ Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁴ Department of Cardiology, Thorax Center, University Medical Center Groningen, Groningen, the Netherlands.
⁵ Department of Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
⁶ Centre d'Investigations Cliniques Plurithématique 1433, French Institute of Health and Medical Research U1116, French Clinical Research Infrastructure Network-Investigation Network Initiative-Cardiovascular and Renal Clinical Trials, Centre Hospitalier Régional Universitaire de Nancy, Université de Lorraine, Nancy, France.
⁷ British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom. Electronic address: john.mcmurray@glasgow.ac.uk.

PMID: 38739064
DOI: 10.1016/j.jacc.2024.03.426

Abstract

Background: Kidney dysfunction often leads to reluctance to start or continue life-saving heart failure (HF) therapy.

Objectives: This study sought to examine the efficacy and safety of mineralocorticoid receptor antagonists (MRAs) in patients with HF with reduced ejection fraction experiencing significant kidney dysfunction.

Methods: We pooled individual patient data from the RALES (Randomized Aldactone Evaluation Study) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) trials. The association between MRA treatment and outcomes was assessed according to whether the estimated glomerular filtration rate (eGFR) declined to <30 mL/min/1.73 m² or not. The primary outcome was cardiovascular death or HF hospitalization.

Results: Among 4,355 patients included, 295 (6.8%) experienced a deterioration of eGFR after randomization to <30 mL/min/1.73 m². These patients had more impaired baseline cardiac and kidney function (eGFR 47.3 ± 13.4 mL/min/1.73 m² vs 70.5 ± 21.8 mL/min/1.73 m²) and had a higher risk of the primary outcome than patients without eGFR deterioration (HR: 2.49; 95% CI: 2.01-3.08; P < 0.001). However, the risk reduction in the primary outcome with MRA therapy was similar in those who experienced a decrease in eGFR to <30 mL/min/1.73 m² (HR: 0.65; 95% CI: 0.43-0.99) compared with those who did not (HR: 0.63; 95% CI: 0.56-0.71) (P_interaction = 0.87). In patients with a decrease in eGFR to <30 mL/min/1.73 m², 21 fewer individuals (per 100 person-years) experienced the primary outcome with MRA treatment, vs placebo, compared with an excess of 3 more patients with severe hyperkalemia (>6.0 mmol/L).

Conclusions: Because patients experiencing a decrease in eGFR to <30 mL/min/1.73 m² are at very high risk, the absolute risk reduction with an MRA in these patients is large and this decline in eGFR should not automatically lead to treatment discontinuation.

Keywords: acute kidney injury; chronic kidney disease; eplerenone; heart failure with reduced ejection fraction; mineralocorticoid receptor antagonist; spironolactone.