Cost-effectiveness of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction: the brazilian case with bayesian networks and markov influence diagrams
Authors: Carvalho L S F , Koeche C , Botelho Y , Bertuol A L , Nunes A V , Oliveira M G S , Dourado L , Andrade J , Magno A , Pacheco A , Nogueira A C C , Guimaraes A J B A , Sposito A C , Fernandez M D , Pfitzner M 
Published: October 2024

Abstract

Background
Heart failure (HF) is one of the leading causes of death worldwide, with a significant burden in middle-income countries, such as Brazil. Mineralocorticoid receptor antagonists (MRAs) have been established as a cornerstone in the treatment of HF with reduced ejection fraction (HFrEF), but their adoption has faced obstacles. Until recently, spironolactone was the only MRA available in Brazil, with restricted use due to associated side effects, such as gynecomastia and hyperkalemia. However, the introduction of new MRAs, such as finerenone and eplerenone, has the potential to change the therapeutic landscape. Understanding the cost-effectiveness of these agents in the Brazilian healthcare context is essential to optimize HF management.

Methods
A Bayesian Network approach complemented by Markov Influence Diagrams was employed to estimate incremental cost-effectiveness ratios (ICERs), presented in international dollars (Int$) gained per quality-adjusted life year (QALYs). Discontinuation rates for MRAs were incorporated into the model, reflecting real-world clinical practice, along with a 5% annual discount rate for both costs and effectiveness. To inform our model, a comprehensive systematic review was conducted, followed by a network meta-analysis (NMA) to assess the comparative effectiveness of ARMs. Data on incident cardiovascular outcomes were derived from a Brazilian real-world cohort of 1,098 patients with HFrEF. All cost assessments were made from the perspective of the Brazilian public health system, with values converted to Int$.

Results
The NMA highlighted that spironolactone [HR:0.75 (95%CI 0.67-0.84)], eplerenone [HR:0.84 (95%CI 0.77-0.93)] and finerenone [HR:0.90 (95%CI 0.82-0.98)] significantly reduced the relative risk of all-cause mortality compared to no MRA utilization. Notably, eplerenone significantly reduced hospitalizations due to HF [HR:0.60 (95%CI 0.41-0.90)] compared to no MRA therapy, with spironolactone and finerenone showing HRs of 0.68 (95%CI 0.40-1.17) and 0.83 (95%CI 0.59-1.15) . The analysis also revealed a notably higher risk of MRA discontinuation for finerenone (22%) and spironolactone (51%) compared to eplerenone. In cost-effectiveness comparisons, finerenone was dominated by alternatives, while eplerenone exhibited an ICER of Int$2,614 (95%CI 1,851-3,470)/QALY when compared to spironolactone. Both spironolactone and eplerenone emerged as cost-effective options when compared to no MRA therapy, with eplerenone being particularly favorable below the willingness-to-pay threshold of Int$8,900 per QALY.

Conclusions
In the Brazilian healthcare context, eplerenone will likely be the most cost-effective MRA compared to spironolactone, offering both a reduction in HF-related hospitalizations and a lower discontinuation rate. These findings underscore the value of integrating cost-effectiveness analyzes into healthcare decision-making processes.