Clinical Evidence and Future Directions for Non-steroidal MRAs in HF

초록

Neurohormonal activation plays a pivotal role in the pathophysiology of heart failure (HF), with overactivation of the mineralocorticoid receptor (MR) contributing to fluid retention and myocardial fibrosis. The RALES and EMPHASIS-HF trials established the efficacy of steroidal mineralocorticoid receptor antagonists (MRAs) in heart failure with reduced ejection fraction (HFrEF), leading to their strong recommendation in clinical guidelines. However, their use remains suboptimal due to concerns over adverse effects such as hyperkalemia and sex hormone-related side effects. Furthermore, their efficacy in heart failure with mildly reduced ejection fraction (HFmrEF) and heart failure with preserved ejection fraction (HFpEF) has remained controversial. Finerenone, a non-steroidal selective MRA, has demonstrated significant cardio-renal protective effects and was recently approved based on findings from two major outcome-driven trials in patients with chronic kidney disease and type 2 diabetes (FIDELIO-DKD and FIGARO-DKD). The FINEARTS-HF trial further provided compelling evidence of its potential benefits in HFmrEF and HFpEF, showing a significant positive impact on clinical outcomes. This lecture will comprehensively review the current clinical evidence supporting non-steroidal MRAs in HF, focusing on key findings from major trials. Additionally, we will discuss their mechanistic advantages over steroidal MRAs, including improved selectivity and a lower risk of hyperkalemia. Additionally, we will explore ongoing and future clinical trials evaluating their broader applicability across different HF phenotypes and their potential role in combination strategies with emerging HF therapies