Public Health Impact and Cost-Effectiveness of Empagliflozin (JARDIANCE®) in the Treatment of Patients with Heart Failure with Preserved Ejection Fraction in France, Based on the EMPEROR-Preserved Clinical Trial.

INTRODUCTION: The efficacy and safety of empagliflozin in the treatment of heart failure with preserved ejection fraction (HFpEF) were demonstrated in the EMPEROR-Preserved trial, which showed a 21% reduction in combined risks of cardiovascular death or HF hospitalization [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.69-0.90, p < 0.001] and a 27% reduction in the total number of HF hospitalizations (HR 0.73; 95% CI 0.61-0.88, p < 0.001) compared with placebo. On the basis of these results, the present study aimed to assess the cost-effectiveness of empagliflozin + standard of care (SoC) compared with SoC alone in the treatment of HFpEF. METHODS: A published Markov model was adapted to compare the health and economic outcomes in France, considering a collective perspective, in patients treated with empagliflozin in addition to SoC versus patients treated by SoC alone. The model simulated the intention-to-treat (ITT) population of the trial, transitioning between four mutually exclusive health states representing the quartiles of the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS). For each arm, the model estimated (over a lifetime time horizon) the economics and the health outcomes (HF hospitalizations avoided, and life years and quality-adjusted life years (QALYs) gained) to calculate the incremental cost-effectiveness ratios (ICERs). The resources used were derived by pairing the FREnch Survey on HF (FRESH) cohort data to French health insurance claims data, and the utilities were derived on the basis of the EQ-5D-5L questionnaire valued on the French tariff. Both economic and health outcomes were discounted at a 2.5% annual rate. RESULTS: The model predicted that treatment of HFpEF patients with empagliflozin would prevent, for 1000 patients treated, 74 HF hospitalizations and 15 deaths attributable to cardiovascular events, resulting on average in a gain of 1 month in overall survival (7.24 versus 7.16 years with placebo) and 0.11 QALYs (6.14 versus 6.03 with placebo). Empagliflozin costs were partially offset by the cost savings from avoided hospitalizations. The ICERs were €18,597 per life year gained and €13,980 per QALY gained. The sensitivity analyses conducted showed that empagliflozin has a 65% probability to be cost-effective under the €25,000/QALY threshold. CONCLUSIONS: The base-case results showed that empagliflozin is a cost-effective strategy for management of HFpEF, in addition to the impact on public health by preventing HF-hospitalizations and deaths in France. Sensitivity analyses suggest that 65% of simulations are under the €25,000/QALY threshold.

Cost-effectiveness of empagliflozin in heart failure patients irrespective of ejection fraction in England.

AIMS: Heart failure (HF) is a complex syndrome commonly categorized into two main phenotypes [left ventricular ejection fraction (LVEF) below or above 40%], and although empagliflozin is the first approved medication with proven clinical effectiveness for both phenotypes, its cost-effectiveness of treating the entire HF population remains unknown. METHODS: The analysis was performed utilizing two preexisting, LVEF phenotype-specific cost-effectiveness models to estimate the cost-effectiveness of empagliflozin in adults for the treatment of symptomatic chronic HF, irrespective of ejection fraction (EF). The results of the phenotype-specific models were combined using a population-weighted approach to estimate the deterministic and probabilistic incremental cost-effectiveness ratios (ICERs). RESULTS: Based on combined results, empagliflozin + standard of care (SoC) is associated with 6.13 life-years (LYs) and 3.92 quality-adjusted life-years (QALYs) compared with 5.98 LYs and 3.76 QALYs for SoC alone over a lifetime, resulting in an incremental difference of 0.15 LYs and 0.16 QALYs, respectively. Total lifetime healthcare costs per patient are £15 246 for empagliflozin + SoC and £13 982 for SoC giving an incremental difference of £1264. The ICER is £7757/QALY, which is substantially lower than the willingness-to-pay (WTP) of £30 000 per QALY used by NICE. The results of the probabilistic sensitivity analyses are in line with the deterministic results. CONCLUSION: Empagliflozin is the first efficacious, approved, and cost-effective treatment option for all HF patients, irrespective of EF. The combined ICER was consistently below the WTP threshold. Therefore, empagliflozin offers value for money for the treatment of the full HF population in England.

Multinational cost-effectiveness analysis of empagliflozin for heart failure patients with ejection fraction >40.

AIMS: Heart failure is a chronic progressive condition, with considerable burden on patients' quality of life and economic burden for the healthcare systems. Before the approval of empagliflozin, there were no proven effective treatments for patients with heart failure with left ventricular ejection fraction (HF LVEF) > 40%. The aim of this study was to evaluate the cost-effectiveness of empagliflozin + standard of care (SoC) compared with SoC alone for patients with HF LVEF > 40%, from the perspective of the healthcare systems of the United Kingdom (UK), Spain, and France, and to quantify the healthcare costs for these patients. METHODS AND RESULTS: A lifetime Markov cohort state-transition model was developed based on discrete health states defined by Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score quartiles to track disease severity. Model inputs relied primarily on the EMPEROR-Preserved trial data or obtained from published literature or country-specific databases, as well as local guidelines for the requirements for the conduct of the economic evaluation of healthcare technologies. The total lifetime cost of receiving SoC per patient was £10 092, €15 765, and €14 958 in the UK, Spain, and France, respectively, which increased by £1407, €1148, and €1485, respectively, with the addition of empagliflozin to the SoC. Empagliflozin + SoC was associated with significantly reduced number of hospitalization for HF or cardiovascular death compared with SoC alone, which was a key driver offsetting its drug acquisition costs. The incremental cost-effectiveness ratio per quality-adjusted life year (QALY) gained was consistently favourable at £14 851, €11 706, and €15 447 in the UK, Spain, and France, respectively. Scenario analysis using the New York Heart Association functional class showed similar results. Probabilistic sensitivity analyses showed more than 50% probability for cost-effectiveness for a willingness-to-pay (WTP) threshold of £/€20 000/QALY for the three countries. CONCLUSIONS: Empagliflozin was found to be the first targeted treatment option that is clinically effective and cost-effective for patients with HF LVEF > 40%. Prescribing empagliflozin with SoC to patients with HF LVEF > 40% is expected to improve clinical outcomes and patients' quality of life and substantially below accepted WTP threshold for the healthcare systems in the UK, Spain, and France.

Hospital Resource Utilization and Costs in Patients with Heart Failure in France.

BACKGROUND AND OBJECTIVES: Heart failure (HF) is one of the leading causes of morbidity and mortality, and economic burden on the healthcare system. The aim of this study was to estimate the current hospital resource utilization and costs for HF patients in France. METHODS: This retrospective cohort study included adult HF patients hospitalized in France between January 1, 2019 and December 31, 2019. Data related to sociodemographic characteristics, number and duration of hospital stays, use of medical procedures or expensive and innovative drugs/medical devices included in the "liste-en-sus", and comorbidities were retrieved from the French national hospital discharge database. Data were further stratified based on the presence or absence of cardiac decompensation, comorbidities, ejection fraction (EF) status, and incident/prevalent patients. RESULTS: In 2019, a total of 430,544 patients were hospitalized in France with HF as a primary or associated diagnosis, with 51.9% male and 48.1% female and a mean age of 79.0 years. More than 75% of the study population was composed of prevalent HF patients. About 3.1% of patients were diagnosed with at least one event of cardiac decompensation during follow-up. Also, 20.2% and 9.9% of patients were identified with preserved and reduced EFs, respectively. The average number and length of hospital stays were 1.7 per patient and 10.4 days per patient, respectively. The annual cost of hospitalization for HF was €8341.3 per patient. Presence of cardiac decompensation at index date or during follow-up, reduced EF, and comorbidities were associated with numerically higher frequency and length of hospitalization, and hospitalization cost. For hospitalization and 'liste-en-sus' medical devices, higher cost was observed in incident than prevalent HF patients, while for 'liste-en-sus' drugs, higher cost was reported in prevalent than incident HF patients. CONCLUSION: This study highlighted the high economic hospital burden of HF in France. More studies investigating different HF patient profiles must be conducted to help determine the main factors of hospital cost for HF.