The aim of this study is to evaluate the cost-effectiveness of 2 different therapies of cardiomyopathy (CM) after COVID -19. The focus of the study is fixed dose combination (FDC) of sacubitril/valsartan and standard therapy in Kazakhstan. This is written from the point of view of the health insurance institution.

Information for the age, gender, CM therapy, number of hospitalizations, COVID-19 infection, and past cardiovascular surgeries of 237 patients with incidents of CM which required a hospitalization after a COVID-19 infection was collected. Selected patients were divided into two groups: the cost of FDC and standard therapy and the annual cost of their therapy was calculated. The incremental cost-effectiveness ratio was calculated by dividing the cost of medication therapy by the number of hospitalizations between the two compared groups. Robustness of the results was tested with deterministic and probabilistic sensitivity analyses. The study was performed in City cardiology centre of Almaty in Kazakhstan during 2020–2022.

Results show that FDC is more costly but more effective, leading to fewer hospitalizations. ICER accounts for €-2,743.08 per hospitalization saved in the group on FDC vs standard of therapy.

Sacubitril/valsartan is cost-effective in ambulatory conditions in comparison with standard therapy of cardiomyopathy after COVID-19 leading to savings due to the decrease in the number of hospitalizations.

Cardiomyopathy, cost-effectiveness, pharmacotherapy, sacubitril/valsartan, COVID-19

Cardiomyopathies (CMs) are a heterogeneous group of pathologies characterized by structural and functional alterations of the heart described in the MOGE(S)classification of the American College of Cardiology/American Heart Association stage and New York Heart Association. (Ciarambino et al. 2021). There are around 620 million people living with heart and circulatory disease worldwide and this number has been rising due to changing lifestyles, an ageing and growing population, and improved survival rates from heart attacks and strokes. Globally, it’s estimated that 1 in 13 people are living with a heart or circulatory disease (British Heart Foundation 2023).

Medication for the treatment of CM involves a variety of therapeutic classes. Fixed dose combination (FDC) of sacubitril/valsartan is one of the most recommended choices, as well as a combination of mono products such as ACE inhibitors, diuretics, ca-channel antagonists, sartans, and beta blockers, depending on the involvement of different functions and concomitant diseases (Cooper et al. 2023). The cost-effectiveness of sacubitril/valsartan is studied in different settings for different population groups but rarely in low-income countries (Ramos et al. 2017; McMurray et al. 2018).

The main reason for hospital admission is heart failure diagnosed by signs and symptoms and demonstrated by at least one objective sign, such as pulmonary rales, peripheral oedema, congestion in a chest radiograph, or a third heart sound. Cost-effective management involves patients’ education (Cline et al. 1998).

The Center for Disease Control (CDC 2023) in the United States has published a list of concomitant diseases associated with severe COVID-19 infections. These include cancer, chronic kidney disease, cardiovascular diseases (coronary heart disease, heart failure and/or cardiomyopathy) (Centers for Disease Control and Prevention 2023). A systematic review of the relation between CM and COVID-19 concluded that cardiac injury and cardiomyopathy were common conditions in patients with COVID-19. Authors suggested that cardiac damage should be considered in managing patients with COVID-19. (Omidi et al. 2021). Therefore, medication treatment of CM after COVID-19 should be as effective as possible to prevent further patient deterioration and for low-income countries should also be cost-effective.

In the large, randomized, double-blind PARADIGM-HF trial, sacubitril/valsartan resulted in a significant improvement in morbidity and mortality in patients with CM, and reduced the risk of CV death or heart failure, hospitalization, as well as all causes of death McMurray et al. (2014). These results situated sacubitril/valsartan as a safe and effective therapy, especially for patients in the high risk category such as COVID-19 patients.

In Kazakhstan sacubitril/valsartan was relatively newly introduced in the practice, and up until that point, standard therapy involved a combination of mono products from different classes. To date, there haven’t been studies in Kazakhstan on the cost-effectiveness of ambulatory therapy of patients with cardiomyopathy after COVID-19 and it was this that provoked our interest in this study (Schreiber et al. 2022).

The objective of this study is to evaluate the cost-effectiveness of 2 different therapies of CM after COVID -19. It compares the FDC of sacubitril/valsartan and standard therapy in Kazakhstan. This paper is written from the point of view of the health insurance institution.

In this study we attempt to analyze the cost-effectiveness of including FDC sacubitril/valsartan to the MC therapy after COVID-19 for patients in Kazakhstan. To the best of our knowledge this is the first study from a national perspective exploring the cost effectiveness of FDC sacubitril/valsartan for the patients with CM in Kazakhstan. It shows that the therapy of patients with CM is cost-effective and saves hospitalizations. The strength of our study lies in the fact that it is observing hospitalized patients with clinically proven COVID-19 infection, or with symptoms after their discharge from hospital. Cline et al. analyzed the cost-effectiveness of an educational program for 190 patients with heart failure and found out that education and self-management reduce hospitalizations.

Several cost-effectiveness analyses of the FDC sacubitril/valsartan have been performed in different country settings. According to McMurrey in the UK settings, the cost per quality-adjusted life-year (QALY) gained for sacubitril/valsartan, was £17 100 (€20 400) in comparison with enalapril for a prevented death; in Denmark, the ICER for sacubitril/valsartan was Kr 174 000 (€22 600), while in Colombia, the ICER was COP$39.5 million (€11 200) per QALY gained in preventing one death case in comparison with enalapril. (McMurray et al. 2018). In the same study was also compared the hospitalization rate for enalapril (n = 3.5) and sacubitril/valsartan (between n = 3.2 and n = 3.01) which resembles our study.

Ramos et al. found out that the incremental cost-effectiveness ratio was €17,600 per quality adjusted life-year (QALY) in the Netherlands. The comparison was made between sacubitril/valsartan and enalapril (Ramos et al. 2017).

Ademi et al. assessed the cost-effectiveness of sacubitril/valsartan compared to ACEIs for the treatment of individuals with chronic heart failure from the perspective of the Swiss health care system (Ademi et al. 2017). They found out that the sacubitril/valsartan strategy showed a decrease in the number of hospitalizations (and lifetime hospital costs thus leading to an ICER of CHF 25 684 per QALY).

The study by Thomas A. et al. compared sacubitril/valsartan and enalapril for treating patients with heart failure and reduced ejection fraction (Gaziano et al. 2016). They chose as main treatment outcomes hospitalizations, and quality-adjusted life-years (QALYs) and calculated the costs, and incremental costs per QALY gained. They modelled that there would be 220 fewer hospital admissions per 1000 patients with HF treated with sacubitril/valsartan vs enalapril over a period of 30 years, thus leading to incremental cost-effectiveness ratio (ICER) of $45 017 per QALY. Results for the same study performed by Jordan B King produced similar results, finding that ICER of $50,959 per QALY over a 40-year period (King et al. 2016). The same methodology for Singapore health care setting led to ICER of SGD 41,019 (USD 30,354) to SGD 1,447,103 (USD 1,070,856) per QALY gained (Liang et al. 2018). Evidently, the FDC combination reduces the number of hospitalizations, which has also been noted in our study, and although the differences might be minimal, the evidence supports this conclusion.

Two other studies performed systematic reviews (Rezapour A.) involving 15 studies comparing sacubitril/valsartan and enalapril in terms of reduced mortality and hospitalization rate. Sacubitril/valsartan produced higher annual and total lifetime costs for all countries under consideration (Thailand, Germany, and USA) and was considered a cost-effective alternative (Proudfoot et al. 2013). The second systematic review was performed by Proudfoot (Rezapour et al. 2022) and focused on modelling studies. It included 44 cost-effectiveness models and 5 HTAs from European decision makers, n = 20; North and South Americas, n = 14; Asia and Australia, n = 10]. Authors concluded sacubitril/valsartan to be a cost-effective therapy in 37/41 models in chronic heart failure patients and 2/3 models in hospitalized patients.

Similar to other studies, we also found that sacubitril/valsartan is a cost-effective therapy in comparison for standard of care in Kazakhstan. The difference is that we focused on patients with CM, and right across the spectrum of diseases involving heart failure. Although the cost of therapy is not reimbursed, our analysis shows that in the majority of cases, the FDC combination will result in fewer hospitalizations, and this will always be under the estimated Threshold for Kazakhstan.

The already pointed systematic review on the relation between CM and COVID-19, which concluded that cardiac injury and cardiomyopathy were common conditions in patients with COVID-19, proves our suggestion that the observed patients are at high risk, and it is worth investing in their therapy (Omidi et al. 2021).

The limitation of our study is in the small sample size of the patients on standard therapy. We can assume that physicians prefer to prescribe sacubitril/ valsartan, as more effective therapy to as many patients as possible because of persistent or past COVID-19 infection. We attempted to reduce this limitation by applying a probabilistic sensitivity analysis, to further strengthen the evidence. The other limitation is in the lack of information about the patients’ adherence to therapy which might have deteriorated due to high co-payment.

The system of compulsory social health insurance (CSHI) in Kazakhstan has been in effect since January 1, 2020. Basic principles of the CSHI system are social orientation. The state pays contributions for 11 million citizens from 15 preferential categories. There is joint responsibility shared between the state, employers, and citizens responsible for the health of the population and providing equal access to medical care. Every insured person has the right to the necessary amount of medical care, regardless of the number of paid contributions, and the money goes to the patient. The patient can express a preference for a particular medical establishment to receive medical services as long as it is a provider of the Fund. The Fund pays medical establishments for medical services only after monitoring the quality and volume of medical care provided, as well as medicines included in the Positive drug list (Katsaga et al. 2012).

Sacubitril/valsartan is cost-effective in ambulatory conditions in comparison with standard therapy of cardiomyopathy after COVID-19, leading to savings due to the decrease in the number of hospitalizations.

This study was funded by the European Union Next-Generation EU, through the National Recovery and Resilience Plan of the Republic of Bulgaria, project N BG-RRP-2.004-0004-C01.