Mineralocorticoid receptor antagonists for the treatment of heart failure and kidney disease: a state-of-the-art review

Chronic heart failure causes significant morbidity and mortality worldwide. Mineralocorticoid receptor antagonists are pivotal in the management of heart failure with reduced ejection fraction, as demonstrated in large outcomes trials that tested the efficacy of the steroidal mineralocorticoid receptor antagonists, spironolactone and eplerenone. There is still debate regarding their use in the management of heart failure with mildly reduced ejection fraction or heart failure with preserved ejection fraction. The nonsteroidal mineralocorticoid receptor antagonist finerenone was recently shown to improve outcomes in heart failure with mildly reduced ejection fraction and heart failure with preserved ejection fraction. This review of clinical trials evaluates the efficacy and safety of steroidal and nonsteroidal mineralocorticoid receptor antagonists for the treatment of heart failure across ejection fraction categories. We discuss the benefits of mineralocorticoid receptor antagonists in treating heart failure, including in the setting of chronic kidney disease, and review the benefits of nonsteroidal mineralocorticoid receptor antagonists in patients with chronic kidney disease who are at risk of developing heart failure. We outline the effect of mineralocorticoid receptor antagonists on serum potassium levels and propose strategies for minimizing the risk of hyperkalaemia. With a focus on clinical trial evidence, this review highlights that mineralocorticoid receptor antagonists have a favourable benefit–risk in the prevention and treatment of heart failure.