In this study, previously published population data of patients with AF in China receiving different oral anticoagulant treatments were included in the Markov model for cost-effectiveness analysis. The weighted average method was utilized in our research. Transition probability data came from randomized controlled trials and the utility values date were from cohort studies or population-based studies. In the real world, many factors[30-32], such as low patient compliance and medication errors, might have influenced disease[33, 34]. Thus, it might be difficult to estimate these factors. Therefore they were not calculated or discussed in our research.
As a common chronic disease, the Markov model is used to simulate the disease’s progression and control, which has certain significance in guiding the long-term clinical use of medications. It has been reported that the age of patients with atrial fibrillation is between 20 and 99 years old[35]. The survival time of patients with atrial fibrillation can be several decades. Therefore we choose a more extended period of 30 years for the cycle simulation.
The cost data of this study includes three aspects: the cost of the drug, the examination fees when taking the drug, and the cost of the treatment after disease occurrence. The cost of drug treatment is based on fixed drug pricing from the Beijing drug procurement platform. The examination fees are the fees set by the medical institution. Both of these two types of fees are state-controlled prices. The cost of treating AF-induced stroke or MI is the average cost listed in the 2018 Chinese Health Yearbook. From the cost of drug treatment alone, the average daily cost of warfarin is 0.04-0.15 $, which is much lower than 4.68 $ for dabigatran 110 mg, 6.02 $ for dabigatran 150 mg, and 4.87 $ for rivaroxaban. However, warfarin needs to monitor the INR regularly for a long time, and each monitoring visit requires consultation and examination fees. After adding these fees, the average treatment cost of warfarin is only 0.39 $, still far lower than dabigatran and rivaroxaban.
The results of this study show that the use of warfarin QALYs is 11.07, and the cost of drug treatment, examination, and disease treatment for 30 years is 5317.31$. Since warfarin has a higher risk of stroke, the cost of treating cardiogenic embolism and subsequent rehabilitation is higher[36, 37], therefore, more effective treatments should be selected. Compared with warfarin, for each additional QALY, the costs are rivaroxaban 5550.18 $, dabigatran (150 mg) 13772.09 $, and dabigatran (110 mg) 7381.07$. In 2017, the per capita GDP of China was 9481.88 $[38]. We take three times the GDP as WTP for further analysis. Rivaroxaban has the highest cost-effectiveness, followed by warfarin. Dabigatran 150mg and 110mg have poor cost-effectiveness. Among them, dabigatran 150mg has an extended advantage, and dabigatran 110mg has an absolute disadvantage. When WTP is lower than 53945.51 yuan, warfarin has the highest cost-effectiveness, which is similar to previous studies in Taiwan[39], South Korea[40], and Hong Kong[19].
Previous foreign studies have shown that all NOACs have cost-effectiveness advantages compared to warfarin. Among them, apixaban has the best cost-effectiveness in preventing stroke in patients with atrial fibrillation. However, because of the latest approval of apixaban in mainland China and limited clinical use, apixaban was not included in the analysis. Rivaroxaban and dabigatran are sold at different prices in different regions, leading to changes in cost-effect results. If the price of rivaroxaban is reduced by 30%, rivaroxaban has a better cost effect. At a willingness-to-pay threshold of £20,000 per quality-adjusted life-year (QALY), all NOACs had the positive expected incremental net benefit (INB) compared with warfarin.
In this study, a single-factor sensitivity analysis was performed using Tree Age Pro 2011 software. With the WTP value of 8452.27 $, tornado plot analysis shows that PwarST (probability of ischemic stroke in warfarin), PwarICH (probability of hemorrhagic stroke in warfarin), Umin (year of quality of life in mildly diseased condition), and Criv (rivaroxaban price) are the most influential parameters for the model. The probability of ischemic stroke with warfarin is the most influential factor in the model.In previous studies, the effective control rate of INR was also an important influencing factor when taking warfarin[41]. When time in therapeutic range ≥65%, the risk of ischemic stroke was reduced by warfarin[19]. However, whether warfarin therapy is well-managed or not,rivaroxaban still has absolute economic benefits. The probability of ischemic stroke in warfarin adjusted from minimum to maximum, the ICER of rivaroxaban is adjusted from 6189.53 $ to 9281.03 $, which is consistent with the analysis of baseline results.
Limitations
Furthermore, several limitations are worthy of discussion in this study. First, our research mainly focuses on the results of the Chinese population, but the number of Chinese population included in these randomized controlled studies is limited. Researches published in China are also non-systematic, therefore the included data is limited, leading to deviations in the results. Especially the conversion rate of different disease states, which is most likely to be affected. Second, in China, the out-of-pocket expenses in the medical process vary significantly among different groups of people. Some people pay the full amount at their own expense, some only pay a small part (paid by medical insurance), and some do not need to pay at all. This social phenomenon may lead to large differences in the choice of therapeutic drugs among different groups of people. Third, although we have included the cost of patients’ medical treatment, examinations, and medicines into the cost part, the cost of caring for patients, and salary loss were not included. Therefore, the disease may underestimate the quality of life of patients.