In addition to this the committee agreed that cross-over studies should be excluded to ensure that potential carryover effects are not confounding the outcome. The committee noted that a prospective randomised registry-based trial in HFPEF was due to start recruiting (Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure With Preserved Ejection Fraction (SPIRRIT) that would help answer the questions in this field. Chronic Heart Failure Treating Heart Failure NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 6.2.4 Mineralocorticoid Receptor Antagonists in HFREF The renin-angiotensin system and its products play a key role in the pathogenesis of heart failure. The final product of this pathway is the neurohormone aldosterone is involved in cardiac fibrosis, sodium retention and other pathways leading to deterioration in heart failure. Mineralocorticoid receptor antagonists (MRA) block the action of aldosterone leading to a potent diuretic effect and may also inhibit aldosterone-stimulated fibrosis in the myocardium. The two licensed MRAs are spironolactone and eplerenone. Studies published since the last update of this guideline in 2010 have investigated whether MRA therapy would result in clinical benefits in the general population of patients with heart failure with reduced ejection fraction (HFREF) as opposed to those post-acute myocardial infarction or with highly symptomatic disease. Nonetheless, MRAs like other drugs affecting the renin-angiotensin- aldosterone pathway (including ACE-Is and ARBs) have the potential to induce adverse events including electrolyte disturbances (particularly hyperkaleaemia) and worsening renal dysfunction resulting in increased morbidity and hospitalisations. Concerns about their adverse effects and uncertainty about their benefits have reduced the uptake of these medications in clinical practice. The aim was to review the evidence for the clinical and cost-effectiveness of MRAs in people with HFREF. 