See also the study selection flow chart in Appendix C, forest plots in Appendix E, study evidence tables in Appendix F, GRADE tables in Appendix H and excluded studies list in Appendix I. The majority of patients in the RALES study268, 350, 351 were not taking beta-blockers as background medication, as the study was conducted prior to beta-blockers being mainstream first line treatment. Because of this, any evidence of a beneficial effect of adding MRAs to first line therapy from this study would likely be overestimated. The evidence has therefore been downgraded for indirectness for the efficacy outcomes where the RALES study makes up the majority of the evidence have been excluded within the current review, because they no longer meet the review protocol. For further explanation please refer to the excluded clinical studies table (appendix I) and the Recommendations and link to evidence. Table 47: Summary of studies included in the review Study Intervention and comparison Population Outcomes Comments EMPHASIS- HF Zannad Intervention: Eplerenone (up to 50 mg / day) Comparison: Placebo People aged 55 years with NYHA class II heart failure and LVEF 30% (or 35% if also QRS duration treatment with ACEI, ARB or both and a BB (unless contraindicated) at the recommended maximum dose. 87% on BB, 93% on ACEI and/or ARB. Patients were within 6 months of hospitalisation for CV reason (or high levels of BNP/NTpro-BNP). Mortality Hospitalisation Adverse events (renal function, hyperkalaemia, hypotension, gynaecomastia/br east pain) Mild heart failure population. Trial was stopped prematurely according to pre-specified rules after a median follow- up period of 21 months. J-EMPHASIS- HF Intervention: Eplerenone (up to 50 People aged 55 Mortality Hospitalisation EMPHASIS-HF trial in a Japanese population. Chronic Heart Failure Treating Heart Failure NICE 2018. All rights reserved. Subject to Notice of rights. 