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  1. Ong SC, Low JZ, Linden S
    Front Pharmacol, 2023;14:1195124.
    PMID: 37342587 DOI: 10.3389/fphar.2023.1195124
    Objective: The aim of this study was to determine the cost-effectiveness of adding empagliflozin to the standard of care versus SoC alone for the treatment of patients with heart failure (HF) with reduced ejection fraction (HFrEF) from the perspective of the Ministry of Health of Malaysia. Methods: A cohort-based transition-state model, with health states defined as Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) quartiles and death, was used to determine the lifetime direct medical costs and quality-adjusted life years (QALYs) for both treatment groups. The risks of all-cause death, cardiovascular death, and health state utilities were estimated from the EMPEROR-Reduced trial. The incremental cost-effectiveness ratio (ICER) was assessed against the cost-effectiveness threshold (CET) as defined by the country's gross domestic product per capita (RM 47,439 per QALY) to determine cost-effectiveness. Sensitivity analyses were conducted to assess the key model parameters' uncertainty in respect to the incremental cost-effectiveness ratio. A scenario analysis was performed using health states as defined by the New York Heart Association classes. Results: Compared to SoC alone, empagliflozin + SoC for the treatment of HFrEF was more expensive (RM 25,333 vs. RM 21,675) but gained more health utilities (3.64 vs. 3.46), resulting in an ICER of RM 20,400 per QALY in the KCCQ-CSS model. A NYHA-based scenario analysis generated an ICER of RM 36,682 per QALY. A deterministic sensitivity analysis confirmed the robustness of the model in identifying the empagliflozin cost as the main driver of cost-effectiveness. The ICER was reduced to RM 6,621 when the government medication purchasing prices were used. A probabilistic sensitivity analysis with a CET of 1xGDP per capita reached 72.9% probability for empagliflozin + SoC against SoC being cost-effective. Conclusion: Empagliflozin + SoC compared to SoC alone for the treatment of HFrEF patients was cost-effective from the perspective of the MoH of Malaysia.
  2. Tan YJ, Linden S, Ong SC
    PLoS One, 2024;19(8):e0305257.
    PMID: 39178204 DOI: 10.1371/journal.pone.0305257
    INTRODUCTION: Empagliflozin demonstrates promising clinical benefits in patients with heart failure (HF). While an early study demonstrates that empagliflozin is cost-effective for treating HF patients with reduced ejection fraction (HFrEF) in Malaysia, its cost-effectiveness for HF with ejection fraction (EF)>40% remains unclear. Therefore, the current study aimed to assess the cost-effectiveness of adding empagliflozin to the standard of care (SoC) for HF patients with EF>40% from the perspective of Malaysian healthcare system. Subsequently, the results were consolidated with the findings for HFrEF to evaluate the cost-effectiveness of empagliflozin when used for all HF patients in Malaysia, irrespective of EF.

    METHODS: A cost-utility analysis was performed using a validated Markov model, which modelled a cohort of adult patients through health states related to symptom severity and functional impairment, to estimate costs and quality-adjusted life-years (QALYs). The influence of model inputs and assumptions, sensitivity, scenario, and subgroup analyses were explored. All costs were expressed in 2022 Malaysian ringgits (RM). Costs and QALYs were discounted at an annual rate of 3.0% as per local pharmacoeconomic guideline.

    RESULTS: The base-case incremental cost-effectiveness ratio (ICER) for HF patients with EF>40% was RM 40,454 per QALY gained. At a cost-effectiveness threshold of RM 47,439/QALY gained, empagliflozin was cost-effective in 57% of replications. The model outcomes were sensitive to inputs related to the treatment effect of empagliflozin in reducing HF-related hospitalisation and cardiovascular mortality, and empagliflozin cost. For the overall HF population, the ICER was RM 29,463/QALY gained.

    CONCLUSION: The findings suggest that empagliflozin is a cost-effective treatment option for the Malaysian HF population, including those with EF>40%. As such, the intervention warrants consideration by the Malaysian healthcare provider to mitigate the burden of HF and address the unmet needs of the EF>40% population.

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