Adverse events associated with early initiation of Eplerenone in patients hospitalized for acute heart failure

Autores da FMUP

• João Pedro Melo Marques Pinho Ferreira

  Autor

Participantes de fora da FMUP

• Kobayashi M.
• Yamashina A.
• Satomi K.
• Tezuka A.
• Ito S.
• Asakura M.
• Kitakaze M.

Unidades de investigação

• Cirurgia e Fisiologia

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Background: The guidelines recommend the initiation or up-titration of heart failure (HF) treatments following an HF hospitalization; however, concerns about adverse events may limit the use of mineralocorticoid receptor antagonists (MRAs). Patient profiles or disease severity might impact adverse events associated with MRA therapy in acute HF. Methods: The EARLIER trial included patients with acute HF who were randomized to eplerenone or placebo over 6 months. Adverse events (i.e., worsening renal function [WRF], hyperkalemia, hypotension, and volume depletion/dehydration) were assessed. HF-related outcome included a composite of all-cause mortality, HF re-hospitalization, investigator-reported worsening HF and out-of-hospital diuretic intensification. Results: In 297 patients (mean age: 67 ± 13 years; 73% males), adverse events were observed: 44.4% experienced WRF (>20% drop in estimated glomerular filtration rate[eGFR] and/or investigator-reported WRF), 8.4% had hyperkalemia (potassium >5.5 mmol/L and/or investigator-reported hyperkalemia), 27.9% experienced hypotension (systolic blood pressure[SBP] <90 mmHg and/or investigator-reported hypotension), and 16.8% had investigator-reported volume depletion/dehydration. Eplerenone vs. placebo did not elevate the incidence of these events (all-p-values>0.0 5). Multivariable analyses revealed that, irrespective of treatment allocation, older age (>7 5 years), prevalent diabetes, symptomatic congestion, and microalbuminuria were associated with increased risk of WRF. Baseline eGFR<60 ml/min/1.73m2 and SBP < 90 mmHg predicted hyperkalemia and hypotension, respectively, while older patients were more likely to experience volume depletion/dehydration. However, these patient profiles did not alter the benefit of eplerenone on outcomes (HR [9 5%CI] = 0.53 [0.29 to 0.97], P = 0.04; all-p-for-interaction>0.10). Conclusion: Eplerenone did not increase adverse events compared with placebo in acute HF. Importantly, disease severity and comorbidity burden greatly influence adverse events, but not benefit from eplerenone. © 2024 Elsevier B.V.

Keywords

• Acute Disease; Aged; Aged, 80 and over; Double-Blind Method; Eplerenone; Female; Heart Failure; Hospitalization; Humans; Hyperkalemia; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Spironolactone; Treatment Outcome; brain natriuretic peptide; eplerenone; eplerenone; mineralocorticoid antagonist; spironolactone; acute heart failure; aged; Article; body mass; dehydration; double blind procedure; drug dose increase; drug efficacy; drug safety; estimated glomerular filtration rate; female; hospital readmission; hospitalization; human; hyperkalemia; hypotension; major clinical study; male; multicenter study; New York Heart Association class; prevalence; randomized controlled trial; risk factor; acute disease; clinical trial; controlled study; drug therapy; epidemiology; heart failure; hyperkalemia; middle aged; treatment outcome; very elderly