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

• Published in: International journal of cardiology Vol. 415; p. 132477
• Main Authors: Kobayashi, Masatake, Yamashina, Akira, Satomi, Kazuhiro, Tezuka, Ayako, Ito, Shin, Asakura, Masanori, Kitakaze, Masafumi, Ferreira, João Pedro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.11.2024; Elsevier
• Subjects: Acute heart failure; Adverse events; Eplerenone; Heart failure; Life Sciences; Mineralocorticoid receptor antagonist; Prognosis; Heart failure; Prognosis; Eplerenone; Adverse events; Acute heart failure; Mineralocorticoid receptor antagonist; heart failure; heart failure acute heart failure eplerenone mineralocorticoid receptor antagonist adverse events prognosis; eplerenone; acute heart failure; adverse events; mineralocorticoid receptor antagonist; prognosis
• ISSN: 0167-5273; 1874-1754; 1874-1754
• DOI: 10.1016/j.ijcard.2024.132477

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. 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. 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). 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. •Eplerenone did not elevate rates of WRF, hyperkalemia, hypotension and dehydration.•Baseline HF severity and comorbidity burden were associated with adverse events.•Eplerenone improved HF outcome, irrespective of adverse event-associated factors.