Cost effectiveness of eplerenone in patients with heart failure after acute myocardial infarction who were taking both ACE inhibitors and beta-blockers: subanalysis of the EPHESUS.
ABSTRACT 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 beta-blockers (beta-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 beta-blockers at baseline.
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 $US3.60 per day (year 2004 value). Bootstrap methods were used to estimate the fraction of the joint distribution of the cost and effectiveness. A net-benefit regression model was used to derive the propensity score-adjusted cost-effectiveness curve. The incremental cost effectiveness of eplerenone in cost per life-year gained (LYG) and cost per quality-adjusted life-year (QALY) gained beyond the trial period was estimated using data from the Framingham Heart Study, the Saskatchewan Health database, and the Worcester Heart Attack Registry. Both costs and effectiveness were discounted at 3%. Although not all resource use could be accounted for, the overall perspective was societal.
As in the overall EPHESUS population, the total direct treatment costs were higher in the eplerenone arm than the placebo arm for patients who were taking both ACE inhibitors and beta-blockers ($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 beta-blockers.
Article: The Economics of Heart Failure[Show abstract] [Hide abstract]
ABSTRACT: The overall annual US medical spending attributed to heart failure is approximately $39 billion. Making choices based on the relative efficiency with which therapies improve health is rational. Angiotensin-converting enzyme inhibitors, β-blockers, aldosterone antagonists, and implantable cardioverter-defibrillators are cost-effective in patients with systolic heart failure. In appropriately selected patients with advanced heart failure, the use of cardiac resynchronization therapy (CRT) devices without defibrillation capabilities (CRT-P) as well as heart transplantation seems to provide good value for money. The relative effectiveness and cost-effectiveness of CRT devices with defibrillation capabilities (relative to CRT-P devices) and left ventricular assist devices remain uncertain.Heart Failure Clinics 01/2013; 9(1):93-106. DOI:10.1016/j.hfc.2012.09.005 · 1.41 Impact Factor
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ABSTRACT: The primary adrenal cortical steroid hormones, aldosterone, and the glucocorticoids cortisol and corticosterone, act through the structurally similar mineralocorticoid (MR) and glucocorticoid receptors (GRs). Aldosterone is crucial for fluid, electrolyte, and hemodynamic homeostasis and tissue repair; the significantly more abundant glucocorticoids are indispensable for energy homeostasis, appropriate responses to stress, and limiting inflammation. Steroid receptors initiate gene transcription for proteins that effect their actions as well as rapid non-genomic effects through classical cell signaling pathways. GR and MR are expressed in many tissues types, often in the same cells, where they interact at molecular and functional levels, at times in synergy, others in opposition. Thus the appropriate balance of MR and GR activation is crucial for homeostasis. MR has the same binding affinity for aldosterone, cortisol, and corticosterone. Glucocorticoids activate MR in most tissues at basal levels and GR at stress levels. Inactivation of cortisol and corticosterone by 11β-HSD2 allows aldosterone to activate MR within aldosterone target cells and limits activation of the GR. Under most conditions, 11β-HSD1 acts as a reductase and activates cortisol/corticosterone, amplifying circulating levels. 11β-HSD1 and MR antagonists mitigate inappropriate activation of MR under conditions of oxidative stress that contributes to the pathophysiology of the cardiometabolic syndrome; however, MR antagonists decrease normal MR/GR functional interactions, a particular concern for neurons mediating cognition, memory, and affect. © 2014 American Physiological Society. Compr Physiol 4:965-994, 2014.Comprehensive Physiology 07/2014; 4(3):965-94. DOI:10.1002/cphy.c130044 · 4.74 Impact Factor
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ABSTRACT: Chronic heart failure (CHF) remains an important cause of morbidity and mortality worldwide. Currently, there are no cost-effectiveness studies of eplerenone use in patients with New York Heart Association (NYHA) class II CHF. We sought to evaluate the cost effectiveness of eplerenone compared with placebo in patients with chronic systolic heart failure and NYHA class II symptoms. A 10-year Markov model with yearly cycles was constructed to evaluate the cost effectiveness of eplerenone compared with placebo, based on data from the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And Survival Study in Heart Failure) study. The model classified subjects into two health states: 'Alive with CHF' and 'Dead'. Information about the cost of disease was derived from Australian Refined Diagnosis-Related Groups (AR-DRG) data. The cost of eplerenone was taken from the Australian Pharmaceutical Benefit Scheme. Utility data were derived from published sources, and a 5 % annual discount rate was applied to future costs and benefits. Over 10 years, and compared with placebo, the model predicted that eplerenone would lead to a saving of 0.5 life-years (discounted) and 0.4 quality-adjusted life-years (QALYs) per person. The net cost was (in Australian dollars [$A]) $A6,117 (discounted) per person. These equated to incremental cost-effectiveness ratios of $A12,024 per life-year saved and $A16,700 per QALY saved. Sensitivity analyses indicated that these results were robust. Eplerenone may represent a cost-effective strategy for preventing morbidity and mortality among patients with chronic systolic heart failure and NYHA class II symptoms.American Journal of Cardiovascular Drugs 03/2014; DOI:10.1007/s40256-014-0066-3 · 2.20 Impact Factor