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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

Abstract

Background

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.

Objective

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.

Intervention

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.

Results

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.

Conclusions

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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References

  1. 1.

    American Heart Association. Heart disease and stroke statistics: 2004 update. Dallas (TX): American Heart Association, 2003.

  2. 2.

    Bart BA, Shaw LK, McCants Jr CB, et al. Clinical determinants of mortality in patients with angiographically diagnosed ischemic or nonischemic cardiomyopathy. J Am Coll Cardiol 1997; 30(4): 1002–8.

  3. 3.

    Hasdai D, Topol EJ, Kilaru R, et al. Frequency, patient characteristics, and outcomes of mild-to-moderate heart failure complicating ST-segment elevation acute myocardial infarction: lessons from 4 international fibrinolytic therapy trials. Am Heart J 2003; 145(1): 73–9.

  4. 4.

    Velazquez EJ, Francis GS, Armstrong PW, et al. An international perspective on heart failure and left ventricular systolic dysfunction complicating myocardial infarction: the VALIANT registry. Eur Heart J 2004; 25: 1911–9.

  5. 5.

    Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999; 341: 709–17.

  6. 6.

    Pitt B, Remme W, Zannad F, et al., Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348: 1309–21.

  7. 7.

    Weintraub WS, Zhang Z, Mahoney EM, et al. Cost-effectiveness of eplerenone compared with placebo in patients with myocardial infarction complicated by left ventricular dysfunction and heart failure. Circulation 2005; 111: 1106–13.

  8. 8.

    List of diagnosis related groups (DRGS), FY2007. Baltimore (MD): Centers for Medicare and Medicaid Services [online]. Available from URL: http://www.cms.hhs.gov/MedicareFeeforSvcPartsAB/Downloads/DRGdesc07.pdf [Accessed 2009 Dec 4].

  9. 9.

    The average Medicare reimbursement rates, FY2001. Baltimore (MD): Centers for Medicare and Medicaid Services [online]. Available online from URL: www.cms.gov/statistics/medpar/shtstay01drg.pdf[Accessed 2007 Jul 20].

  10. 10.

    Mitchell J, Burge RT, Lee AJ, et al. Per case prospective payment for episodes of hospital care. Springfield (VA): US Department of Commerce National Technical Information Service, 1995.

  11. 11.

    Beebe M, Dalton JA, Espronceda M, et al. Current procedural terminology (CPT) 2008: professional edition. Chicago (IL): American Medical Association, CPT Editorial Panel, 2007.

  12. 12.

    2001 Drug Topics: Red Book. Montvale (NJ): Thomson PDR, 2001.

  13. 13.

    Peeters A, Mamun AA, Willekens F, et al. A cardiovascular life history: a life course analysis of the original Framingham Heart Study cohort. Eur Heart J 2002; 23: 458–66.

  14. 14.

    Downey W, Beck P, McNutt M, et al. Health databases in Saskatchewan. In: Ttrom BL, editor. Pharmacoepidemiology. 3rd ed. Chichester: Wiley, 2000: 325–45.

  15. 15.

    Goldberg RJ, Yarzebski J, Lessard D, et al. A two-decades (1975 to 1995) long experience in the incidence, in-hospital and long-term case-fatality rates of acute myocardial infarction: a community-wide perspective. J Am Coll Cardiol 1999; 33(6): 1533–9.

  16. 16.

    Spencer FA, Meyer TE, Goldberg RJ, et al. Twenty year trends (1975–1995) in the incidence, in-hospital and long-term death rates associated with heart failure complicating acute myocardial infarction: a community-wide perspective. J Am Coll Cardiol 1999; 34(5): 1378–87.

  17. 17.

    Blackstone EH, Naftel DC, Turner ME. The decomposition of time-varying hazard into phases, each incoporating a separate stream of concomitant information. J Am Stat Assn 1986; 81: 615–24.

  18. 18.

    Mahoney EM, Jurkovitz CT, Chu H, et al. Cost and cost-effectiveness of an early invasive versus conservative strategy for the treatment of unstable angina and non-ST-segment elevation myocardial infarction. JAMA 2002; 288(15): 1851–8.

  19. 19.

    Dolan P. Modeling valuations for EuroQol health status. Med Care 1997; 35: 1095–108.

  20. 20.

    Mahoney EM, Mehta S, Yuan Y, et al. Long-term cost-effectiveness of early and sustained clopidogrel therapy for up to 1 year in patients undergoing percutaneous coronary intervention after presenting with acute coronary syndromes without ST-segment elevation. Am Heart J 2006; 151: 219–27.

  21. 21.

    Steg PR, Dabbous OH, Feldman LJ, et al. Determinants and prognostic impact of heart failure complicating acute coronary syndromes: observations from the Global Registry of Acute Coronary Events (GRACE). Circulation 2004; 109: 494–9.

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Acknowledgments

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.

Author information

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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Keywords

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