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Cost Effectiveness of Eplerenone in Patients with Heart Failure after Acute Myocardial Infarction Who were Taking Both ACE Inhibitors and β-Blockers

Subanalysis of the EPHESUS



The EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure and Survival Study) showed that the use of aldosterone blockade with eplerenone decreased mortality in patients with heart failure after acute myocardial infarction, and a subsequent analysis showed eplerenone to be highly cost effective in this population.


To assess the cost effectiveness of eplerenone in an EPHESUS subgroup population who were taking both ACE inhibitors and β-blockers (β-adrenoceptor antagonists) at baseline.


In the EPHESUS, a total of 6632 patients were randomized to receive eplerenone 25–50 mg/day (n = 3319) or placebo (n = 3313) concurrently with standard therapy and were followed for up to 2.5 years. Of these, 4265 (64.3%) patients (eplerenone: n = 2113; placebo: n = 2152) were taking both ACE inhibitors and β-blockers at baseline.

Methods and Main Outcome Measures

Resource use after the initial hospitalization included additional hospitalizations, outpatient services, emergency room visits, and medications. Eplerenone was priced at an average wholesale price of $US3.60 per day (year 2004 value). Bootstrap methods were used to estimate the fraction of the joint distribution of the cost and effectiveness. A net-benefit regression model was used to derive the propensity score-adjusted cost-effectiveness curve. The incremental cost effectiveness of eplerenone in cost per life-year gained (LYG) and cost per quality-adjusted life-year (QALY) gained beyond the trial period was estimated using data from the Framingham Heart Study, the Saskatchewan Health database, and the Worcester Heart Attack Registry. Both costs and effectiveness were discounted at 3%. Allthough not all resource use could be accounted for, the overall perspective was societal.


As in the overall EPHESUS population, the total direct treatment costs were higher in the eplerenone arm than the placebo arm for patients who were taking both ACE inhibitors and β-blockers ($US14 563 vs $US12 850, difference = $US1713; 95% CI 721, 2684). The number of LYGs with eplerenone compared with placebo was 0.1665 based on the Framingham data, 0.0979 using the Saskatchewan data, and 0.2172 using the Worcester data. The incremental cost-effectiveness ratio (ICER) was $US10 288/LYG with the Framingham data, $US17 506/LYG with the Saskatchewan data, and $US7888/LYG with the Worcester data (99% <$US50 000/LYG for all three sources). The ICERs were systematically higher when calculated as the cost per QALY gained ($US14 926, $US25 447, and $US11 393, respectively) as the utilities were below 1 with no difference between the treatment arms.


As for the overall EPHESUS population, aldosterone blockade with eplerenone is effective in reducing mortality and is cost effective in increasing years of life for the EPHESUS subgroup of patients who were taking both ACE inhibitors and β-blockers.

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This analysis was financially supported by Pfizer, Inc. The sponsor of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The writing committee had final responsibility for the decision to submit for publication.

Dr Weintraub has received grants from Pfizer, Inc. Dr Willke is an employee of Pfizer, Inc.; his compensation includes stock options. The other authors have no conflicts of interest that are directly relevant to the content of this study.

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Correspondence to Dr Zefeng Zhang.

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Zhang, Z., Mahoney, E.M., Kolm, P. et al. Cost Effectiveness of Eplerenone in Patients with Heart Failure after Acute Myocardial Infarction Who were Taking Both ACE Inhibitors and β-Blockers. Am J Cardiovasc Drugs 10, 55–63 (2010). https://doi.org/10.2165/11319940-000000000-00000

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  • Acute Myocardial Infarction
  • Eplerenone
  • Leave Ventricular Systolic Dysfunction
  • Average Wholesale Price
  • Cardiovascular Hospitalization