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The following is a summary of “Eplerenone, diabetes, and chronic kidney disease in patients hospitalized for acute heart failure: findings from the EARLIER trial,” published in the March 2025 issue of the Cardiovascular Diabetology by Kobayashi et al.

Mineralocorticoid receptor antagonists (MRAs) remain underutilized in the management of heart failure (HF), particularly among patients with comorbid diabetes and chronic kidney disease (CKD). However, the influence of concurrent diabetes and CKD on the efficacy and safety of eplerenone in acute HF has not been well established. This study, based on data from the EARLIER trial, aimed to evaluate the impact of these conditions on cardiovascular outcomes and treatment response. The trial included 300 patients with acute HF who were randomized to receive either eplerenone or a placebo for six months. 

Patients were stratified into groups based on the presence of diabetes and/or CKD, defined by an estimated glomerular filtration rate (eGFR) of less than 45 ml/min/1.73 m² or a urine albumin-to-creatinine ratio (UACR) of at least 30 mg/g. The primary outcomes assessed included cardiovascular death, HF hospitalization, worsening HF, and the need for out-of-hospital diuretic intensification, while adverse events were also monitored across different diabetes/CKD categories. The study population had a mean age of 67 ± 13 years, with 73% being male. Of the participants, 39% had diabetes, and 58% were diagnosed with CKD. The median UACR was 34 mg/g (interquartile range: 13–84 mg/g). 

Notably, patients with both diabetes and CKD, comprising 26% of the cohort, exhibited a significantly higher risk of cardiovascular death and/or hospitalization compared to those without these comorbidities ([HR] = 2.57, 95% CI = 1.29–5.12; P = 0.007). This elevated risk remained significant even after adjusting for confounding factors, such as natriuretic peptide levels (adjusted HR = 2.33, 95% CI = 1.12–4.84; P = 0.02). However, the therapeutic effects of eplerenone on HF-related outcomes were consistent across all diabetes/CKD subgroups, with no significant interaction effects observed (all P-for-interaction > 0.05). Similarly, the safety profile of eplerenone did not vary based on diabetes and CKD status, indicating its tolerability across different patient populations. These findings suggest that while the coexistence of diabetes and CKD significantly increases the risk of adverse cardiovascular events in patients with acute HF, it does not diminish the efficacy or safety of eplerenone therapy. 

This underscores the potential role of MRAs in improving HF management, even in high-risk populations with multiple comorbidities. Future research should further explore strategies to optimize MRA use in this vulnerable patient group to enhance clinical outcomes and reduce HF-related morbidity and mortality.

Source: cardiab.biomedcentral.com/articles/10.1186/s12933-025-02659-y