Budget Impact of Eplerenone for Heart Failure with Reduced Ejection Fraction: National Perspective and Regional Implications in Italy

INTRODUCTION: Heart failure with reduced ejection fraction (HFrEF) represents a major clinical and economic burden in Italy, driven by an aging population. Mineralocorticoid receptor antagonists (MRAs) are a cornerstone of guideline-recommended therapy. Eplerenone has demonstrated efficacy in reducing mortality and hospitalizations but remains underutilized. This study assessed the budget impact of increasing eplerenone use in eligible patients with HFrEF from national and regional perspectives. METHODS: A budget impact analysis (BIA) was conducted over a 3-year horizon from the perspective of the Italian National Health Service (INHS). Two scenarios were compared: Current (observed MRA use) and Projected (increased eplerenone uptake). Model inputs included eligible population, treatment distribution, drug acquisition costs, and clinical outcomes (all-cause mortality, hospitalizations, renal impairment, hyperkalemia, and gynecomastia) with associated costs. Clinical inputs were derived from a network meta-analysis (NMA); cost inputs from Italian literature and national tariffs. RESULTS: Total expenditure increased from €598.6 million (M) to €600.6 M over 3 years, corresponding to a net budget impact of + €2.01 M (+ 0.34%), with annual increments of €880,000 (year 1), €885,000 (year 2), and €245,000 (year 3). Increased eplerenone use resulted in higher costs (+ €35.07 M), driven by drug acquisition and hospitalization costs, partially offset by mortality-related savings (-€3.62 M). These were partially counterbalanced by reductions in other MRAs (spironolactone - €6.37 M, potassium canrenoate - €8.32 M, canrenone - €18.37 M), mainly due to fewer hospitalizations, renal events, and a lower drug volume. Results were primarily driven by clinical parameters for eplerenone, particularly NMA-derived hazard ratios for hospitalization and all-cause mortality. The net budget impact was modest in relative terms (< 0.4% of total MRA-related expenditure), indicating substantial budget neutrality. CONCLUSIONS: Greater adoption of eplerenone was associated with a modest net increase in healthcare expenditure for the INHS, corresponding to approximately €3.20 per treated patient per year and consistent with substantial budget neutrality. The budget impact reflects both treatment redistribution and differences in clinical outcomes across MRAs. Expanding eplerenone use in line with guideline-recommended therapy may be achieved at a limited additional cost, while offering a more favorable renal and selectivity profile relative to other MRAs.