ISBN: 978-1-4731-3093-7 6.2.4.5 Evidence statements Clinical Four studies (reported in 13 publications), comparing MRAs with placebo in people with heart failure with reduced ejection fraction on current standard first line treatment, were identified for inclusion within the review. Three of the studies compared eplerenone with placebo and one study compared spironolactone with placebo. The quality of the evidence ranged from moderate to very low. Evidence was downgraded due to a number of contributory factors including risk of bias, imprecision due to wide confidence intervals surrounding the effect estimate and indirectness of the reported outcomes. Moderate quality evidence was found for the outcomes renal function as measured by a 30% reduction in eGFR from baseline (n=1663) and gynaecomastia as a result of spironolactone use (n=1217), and low quality evidence was found for the outcome hyperkalaemia (n=4786), all of which showed a clinically important harm with the use of MRAs. Moderate quality evidence was also found for the outcomes renal function as measured by change in creatinine (n=2729) and renal function as measured by change in eGFR (n=2737), both of which showed no clinically important effect with the use of MRAs. The outcomes all-cause mortality (n=4621), hospitalisation for any cause (dichotomous) (n=221) and all-cause hospitalisation (n=4400) were rated as very low quality for the first two and low quality for the latter, and showed a clinically important reduction in deaths with the use of MRAs (associated with wide confidence intervals around the effect estimate). The outcome change in NYHA class (n=1456) was rated very low quality and also showed a clinically important benefit with MRA use. Three of these outcomes (all-cause mortality, all-cause hospitalisation and Change in NYHA class Improved) were downgraded for indirectness due to the fact that the majority of people included were not taking beta-blockers as concomitant medication. 