Elsevier

Clinical Therapeutics

Volume 41, Issue 6, June 2019, Pages 1066-1079
Clinical Therapeutics

Cost-Utility Analysis of Sacubitril/Valsartan Use Compared With Standard Care in Chronic Heart Failure Patients With Reduced Ejection Fraction in South Korea

https://doi.org/10.1016/j.clinthera.2019.04.031Get rights and content

Abstract

Purpose

Sacubitril/valsartan, the first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is a possible treatment option for chronic heart failure patients with reduced ejection fraction (HFrEF). The aim of this study was to estimate the cost-effectiveness of sacubitril/valsartan use in South Korea for treating patients with HFrEF compared with that of enalapril, an angiotensin-converting enzyme inhibitor, and with angiotensin receptor blockers (ARBs).

Methods

A Markov model was designed to estimate the lifetime cost-effectiveness of treatment for patients with HFrEF. Cohorts in the alive-state incurred a monthly risk of hospitalization because of deteriorated HF, adverse events (AEs), or death. Transition probabilities of sacubitril/valsartan and enalapril were estimated by using data from the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. The effectiveness of ARBs (eg, reduction in mortality and hospitalization rates) was assumed to be identical to that of enalapril, according to the results of the meta-analysis. However, there was no comparative evidence for AEs. We therefore conducted a Bayesian network meta-analysis and adjusted the incidence rate of AEs for ARBs. The utility for estimating quality-adjusted life years (QALYs) was elicited by the survey of the general South Korean population by using EuroQol-5 dimensions. We calculated the medical costs, including medication, monitoring, hospitalization, AEs, and terminal care, from the health care sector perspective. Costs and effectiveness were discounted by 5%. One-way sensitivity analyses and a probabilistic sensitivity analysis were conducted to determine the model robustness.

Findings

The total cost per patient for sacubitril/valsartan and enalapril was $25,832 and $18,295, respectively. Sacubitril/valsartan was associated with an ∼8- month longer life expectancy compared with enalapril and a QALY gain of 0.59. As a result, the incremental cost-effectiveness ratio for sacubitril/valsartan versus enalapril was $12,722 per QALY. The incremental cost-effectiveness ratio of sacubitril/valsartan versus ARB was $11,970 with an incurred cost of $18,741 for the ARB group. The main results and those of various sensitivity analyses were lower than a threshold of $20,000.

Implications

From a health care sector perspective, sacubitril/valsartan is a cost-effective treatment for HFrEF compared with enalapril and ARBs. This finding could be helpful for cardiologists or decision makers in reaching cost-effective choices regarding the treatment selection process.

Introduction

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have been used for >2 decades to treat heart failure patients with reduced ejection fraction (HFrEF) based on clinical trials showing the efficacy of these medications.1, 2, 3, 4, 5 Despite available pharmacotherapies, HF remains a leading cause of death, with an ∼50% survival rate within 5 years.6 Moreover, patients with HF who were hospitalized because of poor prognosis exhibited a high rate of readmission and mortality, and they incurred additional medical costs, which accounted for one half of the total HF-related medical costs.7, 8 Those unmet needs necessitate new medications to reduce the burden of this illness.

A large, Phase III randomized clinical trial, PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure), showed an improved outcome with sacubitril/valsartan, which is the first-in-class angiotensin receptor neprilysin (ARNI), relative to that of enalapril.9 Sacubitril/valsartan showed a significant reduction in cardiovascular (CV) death and hospitalization for HF compared with enalapril (hazard ratio, 0.80; 95% CI, 0.73–0.87; P < 0.001). In addition, sacubitril/valsartan significantly lowered the risk of readmission relative to that of enalapril.10 Based on this compelling evidence, sacubitril/valsartan became available as an alternative treatment for chronic HFrEF according to the updated guidelines.1

Although the effectiveness of the new medication has been established, the accessibility of new medication is often associated with cost-effectiveness because this factor is an important standard for many countries using health technology assessment to reimburse medication.11 The cost-effectiveness of sacubitril/valsartan has been shown in Western countries, including the United States, the United Kingdom, Denmark, Colombia, and the Netherlands.12, 13, 14, 15, 16, 17 HF is also a substantial health problem in the Asian population18, 19; the cost-effectiveness of sacubitril/valsartan has not yet been proved in Asian countries, although previous studies have been conducted.20, 21

There are additional knowledge gaps from previous studies. First, the cost-effectiveness of sacubitril/valsartan has been identified compared with that of ACE inhibitors, especially enalapril. ARBs had been restricted to patients who were intolerant to ACE inhibitors because of cough or angioedema, or already tolerating ARBs for other indications.22 ARBs are now considered a first-line treatment for patients with HFrEF after the guidelines were revised in 2016.1 Moreover, ARBs are used in a proportion similar to that of ACE inhibitors in Asian countries.23 In particular, ARBs are more commonly used for patients with HF than ACE inhibitors in South Korea.24 Consequently, evidence regarding the cost-effectiveness of sacubitril/valsartan relative to ARBs is necessary. Second, previous studies applied utility values obtained from patients with HF.13, 25 Utility is used for calculating the quality-adjusted life year (QALY), which is the final outcome of effectiveness that reflects the quality of life in pharmacoeconomic studies. Because reimbursement of a new medication is supported by public resources, the utility elicited by the general population is appropriate in terms of reflecting the perspective of the entire society.26, 27

The goal of the current study was to determine the cost-effectiveness of sacubitril/valsartan with consideration of the unidentified points discussed earlier. A cost-utility analysis of sacubitril/valsartan compared with ACE inhibitors or ARBs was therefore conducted by using a South Korean health care setting with QALY estimated according to the utility of the general South Korean population.

Section snippets

Overview of Cost-utility Analysis

According to a systematic review of cost-effectiveness studies of chronic HF treatment, among 33 studies that used decision-analytic modeling, 27 applied the Markov model.28 A Markov model is useful when the interested disease contains a continuous risk over time, such as mortality, or the possibility of >1 major event (eg, hospitalization because of HF deterioration).29 We used a Markov model to estimate the long-term effectiveness and costs of treatment with sacubitril/valsartan and its

Base-Case Analysis

The cost-effectiveness of sacubitril/valsartan use in South Korea was evaluated by applying the proper clinical and cost data (Table I, Table II). According to the results, total QALYs per person over a lifetime horizon were 5.74 and 5.15 for the sacubitril/valsartan and comparator groups, respectively (Table IV). This outcome led to an incremental difference of 0.59 QALY. Calculation of life year gained without utility weights showed that the sacubitril/valsartan and comparator groups gained

Discussion

The current study analyzed the cost-effectiveness of sacubitril/valsartan in South Korea compared with that of enalapril and ARBs. The ICER was estimated by using utilities obtained from the general South Korean population. Although treatment with sacubitril/valsartan is costlier than treatment with the comparators, the ICER did not exceed the South Korean threshold of $20,000 per extra QALY. This outcome might be driven by the fact that sacubitril/valsartan significantly reduces the risk of

Conclusions

We reported the long-term cost-effectiveness of sacubitril/valsartan versus the comparators enalapril and ARBs for HFrEF in South Korea. Our results could be useful for cardiologists in choosing treatments for patients with HFrEF among sacubitril/valsartan and ACE inhibitors or ARBs. Moreover, decision makers could refer to these meaningful results that reflect the preference of the general population.

Conflicts of Interest

Dr. Park, BS. Hong, and Dr. Lee report receiving grants from Novartis Korea Ltd during the conduct of the study. H. Kim, MPH and Dr. S. Kim are employees of Novartis Korea and report that they received personals fee during the conduct of the study. The authors have indicated that they have no other conflicts of interest regarding the content of this article.

The sponsor did not engage in the collection, analysis and interpretation of data, or in the writing of the manuscript.

Acknowledgments

This study was funded by Novartis Korea Ltd. H. Kim and S. Kim are an employee of Novartis Korea, Ltd. The authors indicate no other conflicts of interest regarding the content of this article.

Dr. Park contributed to simulation of the model and writing of the manuscript. Hong contributed to revising the manuscript, and administrative and technical support. H. Kim and S. Kim reviewed the manuscript and contributed to administrative support. Dr. Lee, the study supervisor, contributed to overall

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