Introduction
Cardiovascular diseases (CVDs) are among the top mortality and morbidity causes, globally. During recent decades, the number of lost years by either disability or deaths attributed to CVDs has increased [
1]. Heart valvular disorders (HVDs) including mitral and aortic valves have a direct association with the growing aged population around the world [
2]. Aortic Stenosis (AS) is a prevalent heart valvular problem. The progression of the disease is greater among the aged population [
3].
The disease can increase the risk of death between 25 to 50% at the severe and symptomatic phases. The risk of death can also potentially increase to 90% in five years among those groups of patients who haven’t received appropriate therapeutic actions. It also harms the patients' quality of life (QoL) [
4]. The findings of the quality of life at the symptomatic phase of AS showed that patients are faced with a significant decrease in their physical and social functions. Among elder AS patients (above 65 years) emotional functions, vitality, and mental health have been also degenerated significantly in comparison with the general population [
5].
AS is among diseases with notable direct and indirect costs impact on health systems. The results of a study in the United States showed that symptomatic AS can cause an incremental effect of $12,789 on the annual per-patient healthcare expenditure. At the asymptomatic phase, this incremental effect is $10,816. The annual total attributed costs to symptomatic and asymptomatic AS have been $ 5.6, and $4.6 billion, respectively [
6].
Surgical Aortic Valve Replacement (SAVR) and Transcatheter Aortic Implantation (TAVI) are two commonly recommended interventions for treating AS. SAVR is an invasive open-heart surgery for replacing mechanical or biological prostheses with regurgitating aortic valves. TAVI is known as a minimally invasive procedure (MIP) that takes benefits from technological advancement to replace the broken aortic valve [
7,
8]. The evidence supports the positive impact of Aortic Valve Replacement (AVR) on the improvement of QoL, and cardiac symptoms among elderly groups [
9].
The economic evaluation evidence supports the cost-effectiveness of TAVI as an alternative to SAVR among aged patients who might be at a higher risk for conventional surgery. This evidence is mainly from developed countries including the USA, United Kingdom, Japan, France, Belgium, and Canada. For these high-income countries with a considerable proportion of the senior population, TAVI seems to be a promising procedure that could be cost-effective [
9‐
11]. This evidence has used the results of a large Randomized Controlled Trial which is called PARTNER-1 which enrolled the patients at higher risk of operative procedure [
12]. The cost-effectiveness of TAVI in recent years has been also investigated for the population at the intermediate and low-risk of surgery due to expanding PARTNER-1 and targeting the intermediate and low-risk patients, as well [
13‐
15].
In Iran, SAVR is the more common procedure in managing AS, and it is benefited from the country’s basic health insurance obligations. Cardiovascular disease is the leading cause of death and disability-adjusted life-years in the country. It is also assumed that the prevalence of AS will be growing as the country’s population is aging [
16]. TAVI has been introduced to clinical practice in both public and private healthcare providers in the country. However, as a lower-middle-income country according to the World Bank classification in 2020, the policymakers must know if a technology such as TAVI is cost-effective to be considered in the national health benefit package. Therefore, the purpose of this study is to compare the cost-effectiveness of TAVI with SAVR in managing high-risk elder patients.
Discussion
The cost difference between TAVI and SAVR is 368,180,101 I.R.I Rials (US$ 1,473), and the QALYs difference is 0.37. Also, the cost per QALYs is 995,081,354 I.R.I. Rials (US$ 3,980) for the base case analysis. The base case ICER is greater (~ 1.8 times the country’s GDP per capita as the considered WTP threshold in 2020). The probabilistic sensitivity analysis shows the mean ICER for the strategies is 981,765,302 I.R.I Rials (US$ 3,927) per QALY. In addition, the results of the one-way-sensitivity analysis demonstrate any change between 5 to 150% in stroke risk rate causes a range between 974,642,521 Iranian Rial (US$ 3,898) to 1,365,982,532 Iranian Rial (US$ 5,464) for the base case ICER. This amount of change for the permanent pacemaker implantation rate causes the base case ICER to vary between 973,762,098 Iranian Rial (US$ 3,895) to 1,320,762,751 Iranian Rial (US$ 5,283). This change in myocardial infarction rate leads the base case ICER to lie between 918,541,076 Iranian Rials (US$ 3,674) to 1,243,862,843 Iranian Rial (US$ 4,975). For atrial fibrillation, with the same range of rate change, the base case ICER will be between 975,832,032 Iranian Rial (US$ 3,903) to 1,216,768,043 Iranian Rial (US$ 4,867). Also, if this change considers in the rate of rehospitalization, the base case ICER will be between 942,870,541 Iranian Rial (US$ 3,771) to 1,175,435,431 Iranian Rial (US$ 4,702). The cost-effectiveness probability will be between 31 to 83% by varying the WTP thresholds.
The QALYs for TAVI are greater than SAVR. However, the major issue is related to the attributed costs to TAVI. TAVI is a more expensive procedure, the cost per patient for TAVI is 720,257,876 (US$ 2,881) and for SAVR is 352,077,775 (US$ 1,408), this means TAVI is two times costlier than SAVR. This cost difference can compensate for the greater QALYs advantage that is related to TAVI. In addition, it should be noticed that based on a meta-analysis the main advantage of TAVI in this regard is related to the first thirty days after the procedure, however, at one year follow up there is no difference in QALYs levels between the two procedures [
29].
This is more important in a country such as Iran with economic and financial limitations over the past years. The fall of national exchange rates against other currencies (especially US$, and €) on one side has led to an excessive financial burden on the healthcare providers to use stents, mechanical or biological valves, and TAVI. On the other side, domestic economic challenges such as rising inflation rates have harmed the health system as well. These unprecedented impacts are more obvious in medicines and medical devices dependant procedures. Therefore, presumably, the TAVI procedure has had a hiking price as it includes technologies and devices (especially stents) that have inflated prices.
Fairbairn et al. in their economic evaluation in the UK have concluded that TVI is a dominant cost-effective procedure against SAVR even though its procedural costs make it costlier than SAVR. They also mentioned the post-hospitalization higher costs of SAVR in comparison with TAVI and subsequently the higher QALYs for TAVI vs SAVR [
30]. This conclusion is not the same as what we have found for the Iranian elder population with a higher risk of AS. It seems their time horizon is ten years and by that time there are still alive patients (~ 15% of the cohort), but in our study, we have adopted a lifetime horizon and continue our calculations to the point that there is nobody left alive. In addition, a recent meta-analysis by Cao et al. has found that for patients at higher risk of surgery, the adverse outcomes including stroke, are not different between TAVI and SAVR. This is the same for myocardial infarction and acute renal failure. Generally, they have found that vascular complications are significantly higher in TAVI, but the bleeding is lower in TAVI-managed patients [
31].
Another recently published Health Technology assessment (HAT) in Japan concluded that transfemoral TAVI (TF-TAVI) is a cost-effective procedure for managing the AS among high-risk patients that are not suitable candidates for SAVR [
13].
There are other economic evaluations on using TAVI in managing AS patients, however, the comparators and population of interest are different from ours. In a Markov model economic evaluation by Goodall et al., the results present a 100% probability of cost-effectiveness in favour of TAVI against SAVR at €15,000 willingness to pay threshold. However, the results of this study come from AS patients at the intermediate risk in the PARTNER-II trial with a lower risk for participants [
29]. Watt et al. estimated a likelihood of 100% being cost-effective for TAVI against medical management among AS patients who are not eligible for surgical intervention [
32]. This study has used the PARTNER-I trial data, but for cohort B that means patients are not eligible for conventional surgery.
The important note in this regard is that these studies are from high-income countries that might not be faced with economic problems such as Iran’s specific context issues including paying a higher price for medical devices (here stents, heart valves, pacemakers, and angioplasty) due to sanctions and domestic mismanagement in allocating these resources for managing AS. This condition causes excessive costs that might be reflected in the cost-effectiveness analysis as well.
Limitations
The main parameters for this model especially parameters about the survival rates have been extracted from the PARTNER trial (from the USA, Germany, and Canada), and other risks of post-surgery complications are from developed nations. It may be different from Iran. We tried to capture the impacts of these differences through a one-way-sensitivity analysis and changing the main drivers of base-case ICER, however, it may be still some uncertainties in this regard that only could be addressed through local studies.
Also, the country doesn’t have an explicit cost-effectiveness threshold (or WTP) and in the absence of a revealed WTP, we had to rely on the WHO’s recommendation by using GDP per capita as a basis for it, however, this approach may not demonstrate the actual opportunity cost in the country.
The study has been done in a situation where the country was exposed to substantial financial hardship, and the GDP per capita is one of the lowest over past years, it is quite probable that with changing the macroeconomic situation and subsequently changing in the GDP per capita, the results become different.
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