Weekly Journal Scan: a deep insight into aldosterone antagonism across the heart failure spectrum

Extract

This comment refers to ‘Mineralocorticoid receptor antagonists in heart failure: an individual patient level meta-analysis’ which was published in the Lancet, https://doi.org/10.1016/S0140-6736(24)01733-1.

Comment

Neurohormonal activation, and mostly the renin-angiotensin-aldosterone system, plays a pivotal role in the pathophysiology of HF. Aldosterone antagonists, in combination with ACEi and ARB, are recognized as a cornerstone of the therapy for patients with HFrEF, with a Class IA recommendation in current guidelines.⁶ Despite their proven diuretic, natriuretic, anti-inflammatory, anti-oxidative, and anti-fibrotic effects, the role of MRAs in patients with HFmrEF or HFpEF remains debated, given the non-conclusive results of the trials exploring their benefits in this clinical setting. The TOPCAT trial, published in 2014, assessed the impact of spironolactone in patients with HF and a LVEF ≥45% and showed a non-significant effect on CV death or hospitalization for HF, most likely due to inadequate statistical power to assess a modest treatment effect and a remarkable lack of consistency among the different geographic areas.⁴ This led to a Class IIb recommendation in the European guidelines that suggests considering MRAs to mitigate the risk of HF hospitalization and death in patients with HFmrEF but not those with HFpEF.⁶