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. As a result of this, it is likely that any evidence of a beneficial effect of adding MRAs to first line therapy may have been overestimated for these outcomes. Yet, the outcome hospitalisation for any cause (dichotomous) showed the same effect in a different population albeit with a much smaller sample size (n=221) (associated with wide confidence intervals around the effect estimate). The outcome renal impairment (not defined) (n=221) was of very low quality and showed a clinical benefit of MRA. The remaining outcomes, renal function as measured by increased creatinine (n=226), renal failure (n=2729), gynaecomastia (n=2950) and hypotension (n=3176) were all rated as low or very low quality and showed no clinical effect with MRAs. Economic One cost-utility analysis found that eplerenone in addition to standard therapy is cost effective compared to standard therapy alone for those with heart failure with reduced ejection fraction (ICER: 3,520). This analysis was assessed as partially applicable with potentially serious limitations. One cost-effectiveness analysis found that spironolactone in addition to optimal medical management is more costly and more effective than optimal medical management alone. This was assessed as partially applicable with potentially serious limitations. 6.2.4.6 Recommendations and link to evidence Recommendations Offer a mineralcorticoid receptor antagonist (MRA), in addition to an angiotensin-converting enzyme (ACE) inhibitor (or ARB) and beta-blocker, to people who have heart failure with reduced ejection fraction if they continue to have symptoms of heart failure. [2018] Measure serum sodium and potassium and assess renal function before Chronic Heart Failure Treating Heart Failure NICE 2018. All rights reserved. Subject to Notice of rights. 