Real-World Eligibility and Cost-Effectiveness Analysis of Empagliflozin for Heart Failure in Korea

Abstract

Background: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry.

Methods: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY).

Results: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY).

Conclusion: There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications.

Trial registration: ClinicalTrials.gov Identifier: NCT01389843.

Keywords: Cost-Effectiveness Analysis; Drug Therapy; Empagliflozin; Heart Failure; SGLT2 Inhibitors.

Fig. 1. Comparison of background medical therapies. Background medical therapies were compared between EMPEROR-Reduced, EMPEROR-Preserved trial, and KorAHF registry.

ACEI = angiotensin-converting enzyme inhibitor, ARB = angiotensin receptor blocker, β-blocker = beta-blocker, EMPEROR-Preserved = EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction, EMPEROR-Reduced = EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction, HFpEF = heart failure with preserved ejection fraction, HFrEF = heart failure with reduced ejection fraction, KorAHF = Korean Acute Heart Failure, MRA = mineralocorticoid receptor antagonist.

Fig. 2. Flow chart of empagliflozin eligibility selection. Empagliflozin eligibility were selected based on the inclusion & exclusion criteria of EMPEROR-Reduced and EMPEROR-Preserved trial in HFrEF and HFpEF patients in KorAHF registry.

A-Fib = atrial fibrillation, A-Flutter = atrial flutter, eGFR = estimated glomerular filtration rate, EMPEROR-Preserved = EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction, EMPEROR-Reduced = EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction, HFpEF = heart failure with preserved ejection fraction, HFrEF = heart failure with reduced ejection fraction, KorAHF = Korean Acute Heart Failure, NT-proBNP = N-terminal pro-B type natriuretic peptide, NYHA = New York Heart Association.

Fig. 3. Tornado diagram for one-way sensitivity analysis. The variables are listed in order of influence on economic evaluation. The value of each variable was changed from the base case and shown as the maximum and minimum incremental cost-effectiveness ratio, which are indicated as bars.

QALY = quality-adjusted life year.