ФАРМАКОЭКОНОМИЧЕСКИЕ АСПЕКТЫ ПРОФИЛАКТИКИ ИНСУЛЬТА И СИСТЕМНОЙ ТРОМБОЭМБОЛИИ У ПАЦИЕНТОВ С НЕКЛАПАННОЙ ФИБРИЛЛЯЦИЕЙ ПРЕДСЕРДИЙ: ПРИМЕНЕНИЕ АПИКСАБАНА ПО СРАВНЕНИЮ С ВАРФАРИНОМ И АЦЕТИЛСАЛИЦИЛОВОЙ КИСЛОТОЙ

Background. For prevention of thromboembolic events in patients with non-valvular atrial fibrillation (NVAF) the following types of antithrombotic therapy are used: anticoagulant therapy with vitamin K antagonists (such as warfarin), antiplatelet therapy (such as acetylsalicylic acid) and novel oral anticoagulants such as apixaban, rivaroxaban and dabigatran. Administration of vitamin K antagonists (VKA) is complicated by the need for individual dose adjustment and frequent monitoring of international normalized ratio (INR). Both warfarin and acetylsalicylic acid are widely used for thrombosis prevention in patients with NVAF in the Russian Federation. Aim. To evaluate the cost-effectiveness ratio of apixaban compared with warfarin and acetylsalicylic acid in patients with NVAF from the Russian Federation national health care system perspective. Material and methods. This analysis used a Markov model that allowed estimation of the incremental cost-effectiveness ratio (ICER) for apixaban as compared with warfarin and acetylsalicylic acid over lifetime horizon in VKA suitable and VKA unsuitable patients with NVAF respectively. The model enclosed cardiovascular event rates based on the results of the randomized clinical trials comparing clinical effectiveness and safety of apixaban with warfarin (ARISTOTLE) and acetylsalicylic acid (AVERROES). The following cardiovascular events were taken into consideration: ischemic and hemorrhagic stroke, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds and myocardial infarction. Direct medical costs were determined based on the rates of the compulsory national medical insurance system. The price of the antithrombotic drugs was taken as a weighted average tender price for the year 2013. In the model both costs and benefits (quality-adjusted life years and life-years) were discounted at 3.5%. Cost-effectiveness threshold was set at 1.4 million rubles per quality-adjusted life year (QALY) gained and corresponded to the three times GDP per capita in 2013 in the Russian Federation. Sensitivity analysis explored the impact of the treatment discontinuation rates, patients’ age and quality of INR monitoring on the cost-effectiveness of apixaban. Results. In the base case analysis it was demonstrated that apixaban as compared with warfarin and acetylsalicylic acid provided additional 0.187 and 0.255 life years as well as additional 0.187 and 0.214 QALYs respectively. Over lifetime horizon apixaban as compared with warfarin and aspirin required additional treatment costs equal to 112.72 and 101.35 thousands rubles, respectively. With that estimated incremental cost-effectiveness ratio for apixaban as compared with warfarin and acetylsalicylic acid was 603.92 and 473.02 thousands rubles per QALY respectively. The results were robust in sensitivity analysis. Conclusions. Apixaban is expected to be a cost-effective alternative to warfarin and acetylsalicylic acid in patients with NVAF from the Russian Federation national health care system perspective. Apixaban may be recommended for inclusion into formulary reimbursement lists as an alternative to warfarin.

For prevention of thromboembolic events in patients with non-valvular atrial fibrillation (NVAF) the following types of antithrombotic therapy are used: anticoagulant therapy with vitamin K antagonists (warfarin), antiplatelet therapy (acetylsalicylic acid) and novel oral anticoagulants such as apixaban, rivaroxaban and dabigatran. Along with clinical efficacy and safety profile one of the main characteristics of any medical technology is economic value and cost-effectiveness. The objective of this review was to describe pharmacoeconomic aspects of using apixaban for stroke and other cardiovascular events prevention in patients with NVAF. Results of the previously published cost-effectiveness studies demonstrated that apixaban was projected to increase life expectancy of the patients with NVAF compared with standards of care warfarin and aspirin, novel oral anticoagulants rivaroxaban and dabigatran. At the same time apixaban is expected to be cost-effective alternative from the Russian Federation national healthcare budget perspective.

The treatment of venous thromboembolism with novel oral anticoagulants: warnings and limitations.

Predictors of Warfarin Control in Patients with Atrial Fibrillation in South-East Queensland and Singapore

Clinical experience reversing factor Xa inhibitors with four-factor prothrombin complex concentrate in a community hospital.

Background: The drug therapy of venous thromboembolism (VTE) presents a significant economic burden to the health-care system in low- and middle-income countries. To understand which anticoagulation therapy is most cost-effective for clinical decision-making , the cost-effectiveness of apixaban (API) versus rivaroxaban (RIV), dabigatran (DAB), and low molecular weight heparin (LMWH), followed by vitamin K antagonist (VKA), in the treatment of VTE in China was assessed. Methods: To access the quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs), a long-term cost-effectiveness analysis was constructed using a Markov model with 5 health states. The Markov model was developed using patient data collected from the Xijing Hospital from January 1, 2016 to January 1, 2021. The time horizon was set at 30 years, and a 6-month cycle length was used in the model. Costs and ICERs were reported in 2020 U.S. dollars. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were used to test the uncertainties. A Chinese health-care system perspective was used. Results: In the base case, the data of 231 VTE patients were calculated in the base case analysis retrospectively. The RIV group resulted in a mean VTE attributable to 95% effective treatment. API, DAB, and VKA have a negative ICER (−187017.543, −284,674.922, and −9,283.339, respectively) and were absolutely dominated. The Markov model results confirmed this observation. The ICER of the API and RIV was negative (−216176.977), which belongs to the absolute inferiority scheme, and the ICER value of the DAB and VKA versus RIV was positive (110,577.872 and 836,846.343). Since the ICER of DAB and VKA exceeds the threshold, RIV therapy was likely to be the best choice for the treatment of VTE within the acceptable threshold range. The results of the sensitivity analysis revealed that the model output varied mostly with the cost in the DAB on-treatment therapy. In a probabilistic sensitivity analysis of 1,000 patients for 30 years, RIV has 100% probability of being cost-effective compared with other regimens when the WTP is $10973 per QALY. When WTP exceeded $148,000, DAB was more cost-effective than RIV. Conclusions: Compared with LMWH + VKA and API, the results proved that RIV may be the most cost-effective treatment for VTE patients in China. Our findings could be helpful for physicians in clinical decision-making to select the appropriate treatment option for VTE.

The aims of the study were (i) to examine which antithrombotic therapy patients with known atrial fibrillation use at the point of time when they suffer an ischaemic stroke, (ii) to evaluate the effects of optimal antithrombotic treatment on outcome and severity of the stroke. Patients with known atrial fibrillation before onset of acute ischaemic stroke, and age >60 years were included. Antithrombotic therapy on admission was classified into four groups: no antithrombotic therapy, aspirin, sub-optimal anticoagulation (warfarin and international normalized ratio, INR<2.0) and optimal anticoagulation (warfarin and INR>or=2.0). modified Rankin Scale (mRS) 5 or 6 at day 7 poststroke. (i) death or discharge to a nursing home, (ii) death, (iii) stroke severity on admission assessed by Scandinavian Stroke Scale. A total of 394 patients were included. On admission 109 (28%) patients used no antithrombotic therapy, 169 (43%) aspirin, 52 (13%) warfarin and had an INR<2.0, and 64 (16%) used warfarin and had an INR>or=2.0. The proportion of patients with an mRS 5 or 6 and the corresponding odds ratios were: in the warfarin group with INR<2.0, 16 (31%), OR 3.1 (CI: 1.2-8.0), (P=0.019), in the group with no antithrombotic therapy 29 (27%), 2.5 (1.1-5.9), (P=0.034), and in the aspirin group 41(24%), 2.2 (1.0-5.1) (P=0.054), compared with the warfarin group with INR>or=2.0, where eight (13%) patients had a poor outcome. A significantly higher proportion of patients died or were discharged to a nursing home in the warfarin group with an INR<2.0 (P=0.014), in the aspirin group (P=0.018) and in the no-treatment group (P=0.035), compared with the warfarin group with an INR>or=2.0. No significant differences were found regarding death alone and stroke severity on admission. Few patients with known atrial fibrillation who suffer an ischaemic stroke receive optimal antithrombotic therapy prior to the onset of stroke. Optimal anticoagulation does not only reduce the risk of ischaemic stroke, but also appears to reduce death and severe dependency as well as the need for nursing home care, if an ischaemic stroke occurs.

Aim. To study the structure and incidence of the in-hospital anticoagulants prescription in patients at high risk of thromboembolic events (TEE) and to evaluate clinical characteristics of anticoagulated patients (by the example of the University Clinical Hospital (UCH) №1 of I.M. Sechenov First Moscow State Medical University (FMSMU). Material and methods. The cross-sectional retrospective study held in UCH №1 of the FMSMU, enrolled 677 patients with atrial fibrillation (AF) for whom the prevention of TEE was indicated. Results. Of 677 analyzed cases (women 70%, men 30%) only 61% of the patients received appropriate anticoagulant therapy. Warfarin was prescribed in 73% of the cases, of them unsatisfactory international normalized ratio (INR) control (time in therapeutic range less than 60%) was revealed in 79%. 8.45% of the vitamin K antagonist treated patients developed hemorrhagic complications. 16% of the patients received novel oral anticoagulants (dabigatran – 14%, rivaroxaban – 2%). Bleeding was fixed in 4.2% of the dabigatran treated patients and in 14.3% - in case of rivaroxaban therapy. Conclusion. More than a third of non-valvular AF patients receive inadequate antithrombotic therapy in routine clinical practice. 75% of the anticoagulated patients are prescribed the vitamin K antagonists (typically warfarin) as a traditional anticoagulant. At that, only in 21.7% of the patients receiving vitamin K antagonists, this therapy may be considered adequate. Low incidence rate of the novel oral anticoagulants prescription despite the advantages of such treatment also calls attention.

Atrial fibrillation is associated with development of thromboembolic events. New oral anticoagulants (apixaban, rivaroxaban and dabigatran) are recommended for antithrombotic therapy in patients with non-valvular atrial fibrillation (NVAF) with moderate and high risk of stroke. The objective of this study was to evaluate the cost-effectiveness ratio of apixaban compared to dabigatran and rivaroxaban in patients with NVAF from the Russian Federation national health care system perspective. This analysis used a Markov model that allowed estimation of the incremental cost-effectiveness ratio (ICER) for apixaban compared to rivaroxaban and dabigatran 110 mg and 150 mg over lifetime horizon for patients with NVAF. The model enclosed cardiovascular event rates based on the results of the indirect treatment comparison that combined data from the randomized clinical trials comparing clinical effectiveness and safety of apixaban, rivaroxaban and dabigatran with warfarin (ARISTOTLE, ROCKET-AF, RE-LY). The following cardiovascular events were considered: ischemic and hemorrhagic stroke, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds and myocardial infarction. Direct medical costs were determined based on the rates of the compulsory national medical insurance system. The price of the new oral anticoagulants was taken as a weighted average tender price for the year 2013. In the model both costs and benefits (quality-adjusted life years and life-years) were discounted at 3.5%. Cost-effectiveness threshold was set at 1.4 million rubles per quality-adjusted life year (QALY) gained and corresponded to the three times GDP per capita in 2013 in the Russian Federation. In the base case analysis it was demonstrated that apixaban compared to dabigatran 110 mg and 150 mg and rivaroxaban provided additional 0.101, 0.060 and 0.072 life years as well as additional 0.063; 0.038 and 0.041 QALYs respectively. Over lifetime horizon apixaban compared to dabigatran 110 mg and 150 mg and rivaroxaban required additional treatment costs equal to 22.78; 31.18 and 6.70 thousands rubles, respectively. With that estimated incremental cost-effectiveness ratio for apixaban compared to dabigatran 110 mg and 150 mg and rivaroxaban was 362.60, 805.54 and 162.45 thousands rubles per QALY correspondingly. Apixaban provided increased life expectancy compared to other new anticoagulants and may be considered as a cost-effective alternative to dabigatran 110 mg and 150 mg and rivaroxaban from the Russian Federation national health care system perspective.

Cost-effectiveness analysis in cardiac surgery: A review of its concepts and methodologies

Despite the amount of research performed, the cost-effectiveness of direct oral anticoagulants (DOACs) in subpopulations with different risk factors for stroke has been very little studied. This study aims to explore the cost-effectiveness of the DOACs available in Malaysia in preventing stroke in different subpopulations from a government perspective. An existing Markov model was adapted to assess the cost-effectiveness of the DOACs that are available in Malaysia namely, apixaban (AP), dabigatran (DA) and rivaroxaban (RV). Each was compared with vitamin K antagonists (VKA) in stroke prevention in different patient subpopulations including chronic kidney disease (CKD), high-age, diabetes (DM), and prolonged hospital stay. Cost-effectiveness was assessed by the incremental cost-effectiveness ratio (ICER) benchmarked against the local threshold for cost-effectiveness. The total cost of VKA, AP, DA and RV was Malaysian Ringit (RM) RM9,811 (1USD=RM4.76), RM16,858, RM18,318 and RM20,161 respectively. The quality adjusted life-years (QALYs) gained compared with VKA were 6.11, 6.09 and 6.15 respectively. The ICER when compared with VKA at base case was 57,539, -90,682 and 68,156 respectively. AP had the most favourable ICER at base case. RV had the best ICER compared to AP and DA in patients with CKD and DM at a willingness-to-pay threshold of 1-GDP. Probabilistic sensitivity analysis showed that RV was consistently the most favourable DOAC under a threshold of 2-GDP for all subpopulations. These findings suggested that rivaroxaban has the most favourable ICER in the CKD and DM patient subgroups for stroke prevention among the DOACs available in Malaysia at a threshold of 2-GDP.

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) have been included in international guidelines as important alternatives to vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE) and stroke prevention in non-valvular atrial fibrillation (NVAF). Meanwhile, in the Netherlands, NOACs are widely used next to VKAs. The objective of this study is to estimate the cost-effectiveness of treatment with rivaroxaban compared to VKAs in NVAF and VTE patients in the Netherlands, using data from international prospective observational phase IV studies.Methods: Two models were developed to represent NVAF and VTE patients, populated with patients from the XANTUS (NCT01606995) and XALIA (NCT01619007) international prospective observational studies. The 1-year cost-effectiveness of rivaroxaban use, compared to VKAs, was explored in a population consisting of NVAF and VTE patients (base case) as well as for four scenarios with sub-populations: NVAF patients only, VTE patients only, NVAF patients with unstable international normalized ratio (INR), and NVAF patients using an INR self-measuring device.Results: In the base case, rivaroxaban saved €72,350 and gained 21 quality-adjusted life-years (QALYs) in a simulation of 2,000 patients over the use of VKAs. Ergo, rivaroxaban was dominant over VKAs. The probabilistic sensitivity analysis showed a probability of 85% for rivaroxaban being dominant and 100% at a willingness-to-pay threshold of €20,000/QALY. Rivaroxaban appeared to be dominant in all scenarios as well, except for the NVAF-patients-only scenario where the incremental cost-effectiveness ratio (ICER) was €157/QALY.Conclusions: In patients with NVAF or VTE, rivaroxaban treatment is likely to be cost-effective and a potentially cost-saving alternative to VKA in the Netherlands.

For many years, vitamin K antagonists have been the only oral anticoagulant drugs available for the prevention and treatment of thromboembolic diseases and, thanks to several studies which have consistently documented their high effectiveness, they are still currently used by millions of patients worldwide1. Vitamin K antagonists do, however, have numerous drawbacks, such as delayed onset and offset of action, a narrow therapeutic window, genetic variations of metabolism and interactions with food and drugs that necessitate frequent monitoring of the International Normalised Ratio and dose adjustments1–3. To overcome these limitations, a new class of non-vitamin K antagonist oral anticoagulants (NOA) has been developed in the last decade4. Two types of NOA are currently available: the factor Xa inhibitors apixaban, rivaroxaban and edoxaban and the thrombin inhibitor dabigatran5. In contrast to vitamin K antagonists, which block the formation of multiple active vitamin K-dependent coagulation factors (factors II, VII, IX and X), the NOA block the activity of one single step in coagulation (see Table I for the main characteristics of NOA). The results of several randomised trials and meta-analyses have clearly demonstrated the efficacy of these novel antithrombotic agents in the prevention and treatment of thromboembolism4,6. Table I Main characteristics of novel oral anticoagulants. There are currently two different attitudes to the prescription of NOA, a more permissive one according to which NOA are prescribed to the majority of patients with venous thromboembolism with very few exceptions (i.e., patients with severe renal impairment and patients with cancer) and a more restrictive attitude, which suggests particular caution in the use of NOA mainly because of the lack of antidotes and of comparative efficacy long-term studies (against warfarin) and real-world safety data. These different positions are well represented in the two debates published by Prandoni7 and Riva and Ageno8 in this issue of Blood Transfusion. These papers were presented orally at the last meeting of the Italian Society for the Study of Hemostasis and Thormbosis (SISET) held in Livorno.

The article tells about prevention of ischemic stroke (IS) in patients after IS or transient ischemic attack (TIA) against a background of non-valvular atrial fibrillation (AF). Anticoagulation therapy variants for secondary IS prevention in AF are evaluated, such as vitamin K antagonist warfarin and novel oral anticoagulants: inhibitor of coagulation factor Xa rivaroxaban, apixaban, and the direct thrombin inhibitor dabigatran. There are results of a ROCKET AF subanalysis which compared rivaroxaban and warfarin in patients with AF after IS or TIA. It is noted that widespread clinical use of oral anticoagulants for atrial fibrillation could result in a significant reduction of IS morbidity and mortality in this country.

Relationship of international normalized ratio to bleeding and thromboembolism rates in Taiwanese patients receiving vitamin K antagonist after mechanical valve replacement.