HERTFORDSHIRE MEDICINES MANAGEMENT COMMITTEE

EPLERENONE FOR HEART FAILURE - RECOMMENDED FOR RESTRICTED USE

Name: generic (trade) Indication Date decision Decision NICE guidance last revised status Eplerenone (Inspra ®) NYHA class II chronic heart April 2012 Final NICE – not considered failure SMC – not considered

Eplerenone has recently had a license extension to include the reduction of mortality and morbidity, including heart failure hospitalisation, in patients with New York Heart Association [NYHA] class II chronic heart failure (+ standard therapy).

HMMC Recommendation: Recommended for Restricted use: • Spironolactone should be the first line aldosterone antagonist at all stages of heart failure, with eplerenone reserved for use in patients who have intolerable sex hormone mediated side-effects with spironolactone.

EFFICACY SAFETY • EMPHASIS-HF trial in NYHA class II chronic heart failure: NNT of 13 to • Regular monitoring of serum prevent 1 composite endpoint of death from CV causes or first potassium levels and renal function is hospitalisation for heart failure over median of 21 months. required for aldosterone antagonists. • Aldosterone antagonists spironolactone & eplerenone structurally similar. • Eplerenone has significant potential • No studies vs spironolactone on patient-oriented outcomes. for drug interactions. • Spironolactone is a generic so unlikely to be new trials vs eplerenone. COST PATIENT FACTORS • Eplerenone is much more expensive than spironolactone with estimated yearly costs £555 versus £19. • No cost-effectiveness studies located for eplerenone license extension.

Assessment against Ethical Framework

Evidence of Clinical Effectiveness • EMPHASIS-HF (study upon which the licence extension is based): o high-risk patients with a history of chronic systolic heart failure and mild symptoms (NYHA class II), aged > 55 years (mean age 69 years) and an LVEF < 30% randomised to eplerenone 25-50mg daily or placebo. o Outcome: number needed to treat (NNT) of 13 to prevent one primary outcome (composite of death from CV causes or first hospitalisation for heart failure) over a median follow-up of 21 months. • EMPHASIS-HF was in a very specific patient group. Results may not be applicable to all patients with ‘mild symptoms’. • Aldosterone antagonists sprinolactone and eplerenone are structurally similar. • There are no head-to-head studies of eplerenone versus spironolactone on patient-oriented outcomes in heart failure. • Given that spironolactone is a generic it is unlikely that there will be any new trials vs eplerenone. • Relative benefits provided by spironolactone and eplerenone appear similar for the populations studied.

Cost of treatment and Cost Effectiveness • Eplerenone is much more expensive than spironolactone with estimated yearly costs £555 versus £19, respectively. • No cost-effectiveness studies were located for eplerenone license extension. Approximate annual cost to NHS Hertfordshire for eplerenone license extension could be £200,000 (cost if spironolactone used £7,000).

The Needs of the population • The needs of the population appear to be low as spironolactone is available at a lower cost. However, eplerenone and spironolactone have been studied in different patient groups and there are no relevant head to head studies.

The Needs of the community • Use of eplerenone instead of spironolactone would create a cost pressure which may have an impact on the local health economy which already has to identify savings.

Policy Drivers • Currently no national guidelines on the use of eplerenone for the new indication. • Bedfordshire and Luton Joint Prescribing Group (Feb 2012); pre-licensing recommendation: Spironolactone should be the first line aldosterone antagonist at all stages of heart failure with eplerenone reserved for use in patients who have intolerable sex hormone mediated side effects. Equity References • No impact anticipated. • NICE. Chronic Heart Failure. Clinical Guideline 108. August 2010 http://guidance.nice.org.uk/CG108 • NICE. MI: secondary prevention. Clinical Guideline 48. May 2007 http://guidance.nice.org.uk/CG48 • NPC On the Horizon Future Medicines Evaluation; Eplerenone for patients with NYHA class II chronic heart failure July 2011 Implementability http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Horizon-Scanning/Eplerenone-for-patients-with-NYHA-class-II-chronic-heart- failure/?query=eplerenone&rank=62 • No issues anticipated. • Bedfordshire and Luton Joint Prescribing Committee Eplerenone for NYHA class II chronic heart failure; Feb 2012 • Health Technology Assessment (HTA) (McKenna et al); Aldosterone antagonists for post myocardial infarction heart failure; May 2010; http://www.nelm.nhs.uk/en/NeLM-Area/News/2010---May/26/HTA-Aldosterone-antagonists-for-post-myocardial-infarction-heart-failure- /?query=eplerenone&rank=15 • Ezekowitz JA and McAlister FA. Eur Heart J 2009; 30:469-77 http://www.nelm.nhs.uk/en/NeLM-Area/News/2009---February/16/Systematic- review-Aldosterone-blockade-in-left-ventricular-dysfunction/?query=eplerenone&rank=10 and http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?AccessionNumber=12009103626&UserID=0