The use of mathematical model approach to select direct oral anticoagulants in patients with atrial fibrillation
Authors: Malchikova S.V , Maksimchuk-Kolobova N.S , Kazakovtseva M.V 
Published: November 2020

Abstract

Purpose
To evaluate the clinical and economic effectiveness of direct oral anticoagulants (DOAC) - dabigatran/D, rivaroxaban/R, apixaban/A compared with warfarin/W in the treatment of atrial fibrillation (AF).

Methods
The mathematical model (MM) was used (decision-tree building- DTB) to assess the clinical and economic effectiveness of the DOAC use in comparison with W in the AF treatment. MM was based on the results of basic clinical trials on the use of D (RE-LY); R (ROCKET) and A (ARISTOTLE). MM was carried out on a time horizon of 5 years from the perspective of the healthcare system (HS). The method of cost-effectiveness analysis CER. CER = DC/Ef, CER is the cost-effectiveness balance of the alternative, DC is direct costs, Ef is the number of adjusted life years (ALY) and adjusted life years without complications (ALYC). Budget Impact Analysis. BIA = S (1) − S (2), BIA is the result of the analysis of “impact on the budget”, in monetary terms; S (l) – the total economic effect of the use of one drug, in monetary terms; S (2) – the total economic effect of the use of another drug, in monetary terms. Analysis of “lose opportunities”. MOA = ΔS/Costmin, MOA is the result of the analysis of “lose opportunities”, ΔS is the difference in the total economic effects of the two compared drugs, Costmin is the cost of using the lowest cost drugs.

Results
The MM showed that as a result of pair-wise comparison the DOAC and W, the greatest DC were in group of treatment with the W. The total costs when using D were 10.3% less and amounted to 4129711 against 4605164 rub. per 100 patients. The cost of using R is 5.2% less (4887744 against 5156589); using A by 10.9% (3946528 against 4433820). The greatest difference was due to the different costs of adverse drug reaction treatment (30–38% in the cost structure). In the D group, this cost component was less than the W -by 22.0%, in the R – by 10.9%, in the A – by 36.8%. Costs associated with ischemic stroke treatment were less then 28.1% in the D group. The strategy of using DOAK compared with W allows to provide a greater number of ALY and ALYC – 4, 34 and 4.3 when comparing D and W, 4.3 and 4.25 when R and W; and 4.25 and 4.2 – A and W. ALYC respectively – 3.92 and 3.79; 3.51 and 3.6; 3.9 and 3.74. The cost of ALY is 9516.65 against 10706.45 rub; 11,374.34/12123.81; 9,295.19/10547.31. The cost of ALYC respectively: 10,534.98 against 12150.83 rub.; 13,925.20/14733.11 and 10119.3/11855.13. The use of DOAK allows to save significant public funds, and the savings saved allow to treat the patients in addition by modern drugs. Savings up to 12% in 5 years, while up to 33 patients out of 1000 can be treated additionally.

Conclusion
DC resulting from the prevention of thromboembolic complications when using DOAC in comparison with W can be reduced by 28.1%, hemorrhagic complications by 36.8%. DOAC can save a greater number of ALY and ALYC at a lower cost.

Funding Acknowledgement
Type of funding source: None