Search

Aim. To compare the effectiveness of direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (AF) for preventing stroke and systemic thromboembolism (embolism in the vessels of the systemic circulation, systemic embolism) in terms of pharmacoeconomic indicators. Materials and Methods. The economic assessment was carried out from the standpoint of the healthcare system of the Russian Federation. We used published data on the clinical efficacy and safety of DOACs, which were obtained earlier in clinical trials. The efficacy of therapy was assessed by the incidence of ischemic stroke (IS) of systemic embolism (SE), while the safety was assessed by the incidence of major bleeding (MB) and clinically signifi cant minor bleeding (CSNMB). The total cost of patient management for each alternative treatment option included both the cost of drug therapy and the cost of managing adverse events over a study horizon of 12 months. The conclusion about the most preferred alternative was made on the basis of the ratio of effectiveness and cost of treating the patient. Results. The use of apixaban to prevent IS or SE in patients with AF was accompanied by a decrease in the incidence of their development (HR 0.80, 95 % CI 0.73–0.89; HR 0.72, 95 % CI 0.60–0.85 — compared with rivaroxaban and dabigatran, respectively), as well as a decrease in the frequency of MB compared with other DOACs (HR 0.55, 95 % CI 0.53–0.59; HR 0.78, 95 % CI 0.70–0.87 — compared with rivaroxaban and dabigatran, respectively). Since apixaban was more effective and safer than rivaroxaban and dabigatran, a cost-effectiveness approach was applied in this study. The least expensive treatment regimen included apixaban, the direct cost was 33,263 roubles per patient. The advantage was achieved both due to the lower of therapy with apixaban (29.6–34.0 % lower than other DOACs) and the minimum cost of managing the adverse events: for MB and CSNMB, it was reduced by 20.7 % compared to dabigatran and by 44.7 % compared to rivaroxaban; for stroke/SE, it was reduced by 25.9 % and 20.6 %, respectively. Conclusion. In patients with AF, apixaban was more cost-effective compared with rivaroxaban or dabigatran for preventing IS and SE, as it led to higher clinical efficacy and safety while requiring less healthcare system costs.

Aim. To conduct a pharmacoeconomic analysis of the use of the drug Eliquis® (apixaban), belonging to direct oral anticoagulants (DOACs), for the treatment and prevention of deep vein thrombosis (DVT) and/or pulmonary embolism (PE), including in patients suffering from cancer disease compared with other anticoagulants. Materials and Methods. The economic assessment was made from the standpoint of the healthcare of the Russian Federation. Comparative evaluation of the effectiveness of DOACs was carried out on the basis of the combined rate of the incidence of VTE and death from VTE, as well as death from any cause. Safety assessment — based on the rate of major bleeding (MB) and clinically significant non-severe bleeding (CSNSB). The evaluation was performed on the basis of data obtained in the course of previously performed meta-analyses, the results of which were published. The total cost of patient management for each of the compared alternative treatment tactics was estimated by calculating the cost of a course of drug therapy, as well as the cost of managing adverse events in the study horizon, which was 12 months. The conclusion about the most preferred alternative was made on the basis of data on the relationship between the effectiveness and cost of treating the patient. Results. Apixaban compared with dabigatran and rivaroxaban was associated with a lower risk of developing MB and CSNSB. In addition, in patients taking apixaban, there was a trend towards a decrease in the risk of death from any cause compared with patients who used dabigatran and rivaroxaban, which did not reach statistical significance, which in turn led to the choice of the method of pharmacoeconomic analysis — “cost minimization”. It has been established that the use of apixaban is characterized by the lowest costs, the cost of managing one patient amounted to 59 271,89 rubles per year, which is 28,8 % and 27,2 % lower than similar costs for treatment regimens with the original drugs dabigatran and rivaroxaban, respectively. The difference in costs was due to both the cost of treating complications (1362.8 rubles vs. 2536.3 rubles vs. 3170.9 rubles for apixaban, rivaroxaban and dabigatran, respectively), and the cost of treatment and prophylaxis of DOACs (31 514,20 RUB vs 46 434,8 RUB vs 46 790,6 RUB, respectively). Similar results were achieved in the group of patients suffering from oncological diseases, as DOACs also allowed to reduce costs by 4–5 times compared with the use of LMWH. Conclusion. Among the original DOACs and traditional LMWH therapies, the apixaban regimen has the best cost-effectiveness ratio and is the most preferred alternative in terms of pharmacoeconomic analysis.

In last years, special attention has been paid in the Russian Federation (RF) to improving medical care for patients with atrial fibrillation (AF) and the prevention of thromboembolic complications (TEC). The appearance on the Russian market of new oral anticoagulants (NOAC) has become a help for doctors, however, their cost imposes restrictions on the use. A humanitarian aid drugs to medical organizations of the RF, an active information program from manufacturers over the past 1.5 years have significantly increased the use of NOAC. In different regions, a different situation arises regarding the procurement and frequency of use of one or another anticoagulant. Analyzing the procurement of additional drug supplies for different regions of the Russian Federation, we see that dabigatran is preferred in a number of regions of the Central Federal District, and rivaroxaban in the Northern regions. The cost of warfarin is low. Data on the important role of the genotype in determining the individual dose and the development of bleeding, which is associated with the metabolism of warfarin, have been obtained. The pharmacogenetic approach allows you to quickly and efficiently choose its dose. The use of generics is highly relevant on the Russian market. Also, a number of regions are of great interest as a basis for conducting clinical trials of drugs. Aim. To analyze the current use of anticoagulant drugs taking into account personalized treatment approaches (the implementation of pharmacogenetic examinations and the work of anticoagulation clinics). Methods. Analysis of real clinical practice in the Russian Federation, patient registries, evaluation of adverse events in anticoagulation therapy and pharmacogenetic studies. Analysis of anticoagulant purchase under the Drug Reimbursement Program in several regions of the RF. Evaluation of the effect of anticoagulation clinics throughout the RF. Results. We analyzed the use of anticoagulants. To reduce the risk of thromboembolic complications and select the appropriate antithrombotic therapy, the entire range of antithrombotic agents is required, including NOACs and vitamin K antagonists (warfarin). Th e appearance of warfarin and NOACs on the Russian market has significantly improved the quality of medical care and treatment outcomes in these patients. Active awareness raising, the addition of anticoagulants to the national clinical guidelines and to clinical practice, and state support as part of the Drug Reimbursement Program have significantly increased the frequency of anticoagulant use. Nevertheless, the frequency of anticoagulant use varies slightly between regions. Warfarin is the most widely used anticoagulant and has high affordability (from 44 to 72.5 % out of all anticoagulants). The frequency of bleeding does not differ significantly between different anticoagulants, with an average of 2.8 %. A first INR value of ≥2.0 aft er 3-5 days is significantly associated with over coagulation during warfarin dose titration. The rapid achievement of an anticoagulation effect is often associated with a specific genotype (CYP2C9*2/*2, *3/*3 and 2/*3 variants and A/A of the VKORC1 gene, or CYP2C9 and VKORC1 polymorphism). Pharmacogenomics-guided warfarin dosing in clinical practice allows the warfarin dose to be selected in a faster and more effective way and for the risk of adverse reactions to be reduced. The creation of a network of anticoagulation clinics has proven to be highly effective. The most well-structured system of anticoagulation clinics is present in the Kursk Region. Rivaroxaban was the biggest selling anticoagulant out of the NOACs on the Russian sales market in 2018, but given the growth in apixaban sales, it is likely that this NOAC will move into first place in the near future.Conclusion. A personalized approach to anticoagulant use is crucial for the prevention of thromboembolic complications.

In 127 patients with atrial fibrillation (AF), the efficacy and safety of anticoagulant treatment for 12 months was studied. The mean age of patients was 69.9 ± 1.2 years, 41.7% were older than 75 years, and 20% had GFR

Все още острия исхемичен инсулт (ОИИ) и трайните увреждания в резултат от него имат сериозни социални последици за обществото ни. Задълбочава се необходимостта от нарастване на полаганите усилия от страна на общопрактикуващите лекари, кардиолозите и невролозите у нас по отношение на първичната и вторичната профилактика на мозъчните инсулти. Вече втора година наблюдаваме стабилно подобрение в данните за специфичната терапия на ОИИ в страната ни, но все още резултатите са далеч от препоръчваните към момента от водещи международни организации за лечение на инсулти като например Европейската организация за инсулти. Директните орални антикоагуланти са широко прилагани за вторична профилактика на исхемичен инсулт при пациенти с ПМ, но при редовен прием са противопоказание за провеждане на интравенозна тромболиза. Това оставя ендоваскуларното лечение единствен шанс за рекализационна терапия при тези болни, но за съжаление в България все още има само 4 лечебни заведения, които могат да го реализират. Основното изискване това да се случи до 6 часа от началото на симптомите на ОИИ прави процедурата неприложима в голяма част от тези случаи. За това наличието на специфичен антидот (Идаруцизумаб) за един от ДОАК (Дабигатран) от една страна прави възможно провеждането на интравенозна тромболиза при тези болни, а от друга дава предимство на Дабигатрана при избора на ДОАК за вторична профилактика. Резултатите от литературната справка при тези случаи, както и тези от практиката ни в нашата клиника, показват сравнима ефективност и честота на усложненията спрямо общата група на болни с интравенозна тромболиза, което дава безспорно основание за придържането към този терапевтичен подход.

One of the main causes of death and disability in the world are the thrombotic complications. Using of anticoagulants is the effective method of preventing of these life-threatening conditions. However, the use of anticoagulants involves a significant risk of the bleeding. Safety of anticoagulants predominately are determined by the availability of specific antidotes. Until now new oral directly acting anticoagulants do not have any specific antagonists. Idarutsizumab is the dagibatran-specific antagonist which increases its safety.

Aim: Data on the use of novel anticoagulant drugs (NOACc) in renal transplant recipients is scarce. The aim of our study was to investigate the safety and efficacy of NOACs in renal transplant recipients. Materials and Methods: In a single-centre retrospective cohort study we assessed adverse reactions, thromboembolic events, and interactions of calcineurin inhibitors in patients treated with NOACs. Results: Twenty-three renal transplant recipients were treated with NOACs (70% male), mean age of 65.8 ± 1.8 years. Fourteen (61%) patients were treated with rivaroxaban, apixaban was given to 8 (35%) of our patients, and dabigatran to one patient (4%). The main indications for NOAC therapy was atrial fibrillation in 61% and deep venous thrombosis in 23% of patients. Bleeding occurred in 2 patients (1 treated with rivaroxaban and 1 with dabigatran). None of our patients developed thrombosis while treated with NOAC. During the median follow-up of 24 months graft function, as well as hematological parameters, remained stable in patients that were treated with rivaroxaban and apixaban, while dabigatran was ceased after a month of therapy due to a bleeding event. Conclusion: Our results show that both rivaroxaban and apixaban are safe and efficient oral anticoagulant drugs in renal transplant patients. Additional studies are needed to prove these results. [ABSTRACT FROM AUTHOR]

Venous thromboembolic complications (VTEC) are a frequent pathology accompanied by high lethality. After VTEC the risk of their recurrence not equivalent for all patients remains. The anticoagulant therapy available currently effectively prevents VTEC increasing a possibility of hemorrhages. This means that at planning the secondary prevention it’s necessary to maintain the optimal balance between a possibility of recurrence of VTEC and development of hemorrhagic complications. Thus, selection of patients for secondary prevention must be accompanied by a comprehensive analysis of numerous factors as determining the possibility of VTEC recurrence as well as a risk of complications development. Warfarin is the most frequently used drug for long-term anticoagulant per os therapy, it requires frequent monitoring with periodic dose correction and strict dietary limitations. New oral anticoagulants (NOAC) are applied at a fixed dose without obligatory strict hemostasiologic control, which makes them rather attractive for continues secondary prevention of VTEC.

Фибрилляция предсердий (ФП) является наиболее частым кардиальным источником системной эмболии и кардиоэмболического инсульта. «Новые» пероральные антикоагулянты рекомендованы для предотвращения инсульта у больных с неклапанной ФП и снижения сердечно-сосудистой смертности. Их эффективность подтверждена как в рандомизированных исследованиях, так и в реальной клинической практике.

В статье обсуждаются современные представления о подходах к антитромботической терапии после острого коронарного синдрома (ее длительность, сочетание препаратов, особенности в различных клинических ситуациях).

New data and perspectives of antithrombotic therapy are highlighted in patients with atrial fibrillation. Factors of warfarin therapy efficacy, as well as the possibility of new antithrombotic drugs are considered. Special attention are paid to the direct thrombin inhibitors — dabigatran. Possibilities and usage prospects of dabigatran in patients with atrial fibrillation are discussed in detail in the light of new results of RE-LY trial.

Dabigatran is the new oral anticoagulant that directly inhibits thrombin (factor IIa). In RE-LY clinical trial dabigatran 150 mg b.i.d was more effective than warfarin in prevention of ischemic stroke and systemic embolic events in more than 18000 patients with nonvalvular atrial fibrillation. At that time dabigatran and warfarin showed similar safety. Practical issues of dabigatran treatment, e.g. therapeutic indications, choice of dosage etc. are discussed.

This article discusses the significant features and use of new oral anticoagulant dabigatran etexilate for the treatment of venous thromboembolic complications (VTC). The article presents the results of 4 randomized clinical studies: RE-COVER, RE-COVER II, RE-MEDY and RESONATE. The RE-COVER and RE-COVER (II) studies compared the effectiveness and safety of dabigatran and warfarin in patients with acute episode of VTC, and RE-MEDY and RESONATE studies assessed the prolongation of dabigatran therapy in patients with VTC, who completed the main 3-6-month course of anticoagulant therapy. In addition, REMEDY study estimated efficacy of dabigatran compared with warfarin, and RE-SONATE study estimated one compared with placebo. RE-COVER, RE-COVER II and RE-MEDY showed that the efficacy of dabigatran (150 mg 2 times a day) for the prevention of recurrent and fatal episodes of VTС was not less than that of warfarin; on top of that, dabigatran was more efficient in reducing the risk of hemorrhag-ic complications. In RE-SONATE study, dabigatran showed a 92% reduction in risk of the VTC relapse compared to placebo, but a 2.9-fold increase in risk of large or small clinically significant bleeding.

Indirect comparisons of new oral anticoagulants are performed with focus on their safety. Apixaban, an oral inhibitor of Xa factor, nowadays can be considered as a drug with very good safety profile according to randomized trials results and performed indirect comparisons.

Comparative analysis of oral anticoagulants (vitamin K antagonists and new drugs, including dabigatran, rivaroxaban and apixaban) is presented from the standpoint of safety. The safety profile of the new oral anticoagulants is significantly better than vitamin K antagonists profile, but requires consideration of special clinical situations that predispose to an increased risk of bleeding.

The clinical significance of the patient genetic characteristics in the individual pharmacological response to oral anticoagulants is considered. Possible tactics of warfarin dosing and new oral anticoagulants choice on the basis of pharmacogenetic testing as well as indications for this approach in clinical practice are discussed. It should increase efficacy and safety of anticoagulant therapy.

Atrial fibrillation (AF) is a risk factor for thromboembolic complications, requiring administration of vitamin K antagonists (warfarin) or the new oral anticoagulants (apixaban, dabigatran and rivaroxaban).Aim. To assess the influence of apixaban use on the budget as an alternative to warfarin, dabigatran or rivaroxaban use in patients with non-valvular AF in the Russian Federation (RF).Material and methods. The analysis was performed with the perspective of the health care budget with 5 year horizon period and by the pharmacoeconomic model developed by Pharmerit International (Rotterdam, Netherlands) and adapted for the RF. The cardiovascular complications rate in the model was in line with the results of comparative clinical trials: ARISTOTLE, AVERROES, RE-LY, ROCKET-AF. The analysis suggested that 100% of patients with atrial fibrillation were transferred on apixaban instead of warfarin, dabigatran or rivaroxaban. The analysis was based on the assumption that patients were fully committed to the therapy over the horizon of the study, ie, refusal of treatment was not considered. The possibility of episodes of ischemic and hemorrhagic strokes, the severity of which corresponded to previously published data for the Russian population, was considered in the study. The present study was performed based on two scenarios. In the first of them the cost of anticoagulation therapy was determined on the basis of the average weighted prices of public procurement for the period from 04.01.2014 to 01.04.2015. The alternative scenario purported to demonstrate potential savings of the budget of the health care system on the inclusion of apixaban in the list of essential drugs. This scenario took into account that the cost of dabigatran and rivaroxaban corresponded to registered maximum selling price including 10% VAT and 10% of the wholesale allowance and the cost of apixaban - presumed maximum selling price which the producer intends to register in case the drug is included in the essential drugs list, subject to 10% VAT and 10% wholesale mark. The cost of complications treatment corresponded to the rate of compulsory health insurance for the city of St. Petersburg for 2015.Results. The estimated number of patients with non-valvular AF who require anticoagulation therapy in the RF is 1,196,600 people according to the epidemiological data. Treatment with apixaban significantly reduces the incidence of cardiovascular events as compared with warfarin and rivaroxaban. The results of the budget impact analysis, taking into account the price obtained at auction from 01.04.14 through 01.04.15, show a decrease in the load on the budget when the apixaban is included in the therapy regimen of non-valvular atrial fibrillation. Potential savings of resources of the health care system reached 10.9 billion rubles as compared with dabigatran and 39.2 billion rubles as compared with rivaroxaban. This advantage can be explained by both the lower cost of apixaban in comparison with reference drugs, and a reduction of the in-hospital expenses on complications treatment. Switching from warfarin to apixaban increases the budget load in 2.81 times. However, previous data demonstrate the economic feasibility of the additional costs of apixaban, that help to achieve significant advantages from a clinical point of view. The results obtained on the basis of prices, intended to include apixaban in the list of essential drugs, showed that in this case the savings of the budget of the health care system will reach 127-129 bln. rubles for 5 years (average 26%) as compared with dabigatran and rivaroxaban. The comparison of apixaban with warfarin showed an increase in total costs of therapy in 2.72 times.Conclusion. The inclusion of apixaban in the therapy regimen of non-valvular atrial fibrillation can significantly reduce the burden on the budget of the health care system as compared with dabigatran and rivaroxaban, as well as reduce the incidence of cardiovascular events compared with warfarin. This allows recommending the inclusion of the drug in the federal and regional programs for the prevention of thromboembolic complications in this group of patients.

Data on the problem of thromboembolic complications in non-valvular atrial fibrillation are presented. Peculiarities of anticoagulant therapy to prevent thromboembolic complications, the difficulties in drug choice and dosage adjustment are also discussed.

Aim. To compare direct medical costs of dabigatran and warfarin therapy in patients with non-valvular atrial fibrillation (NVAF) during preparation for elective cardioversion. Material and methods. An open non-randomized study was conducted to evaluate direct medical costs (cost of drug, cost of the international normalized ratio (INR) adjust- ment in outpatient clinic, cost of visits to cardiologist). Patients (n=62) with persistent NVAF (AF paroxysm duration > 48 hours) were enrolled. All of them requested medical as- sistance and were decided to perform an elective cardioversion. The patients received warfarin (n=32) or dabigatran (n=30). The patients of the both groups were similar in the main clinical characteristics and thromboembolic risk levels according to CHA2DS2-VASc scale.Results. Treatment duration before elective cardioversion was 21±2 and 30.5±4.5 days for dabigatran and warfarin groups, respectively (p

В обзорной статье рассмотрены результаты наблюдательного когортного исследования Medicare, целью которого являлось получение дополнительной информации об эффективности и безопасности дабигатрана у более чем 130 тыс. пожилых (старше 65 лет) больных с неклапанной фибрилляцией предсердий, имеющих право на получение бесплатной медицинской помощи в системе Medicare (США). Полученные результаты совпадают с данными, полученными ранее в исследованиях RE-LY и RELY-ABLE, и свидетельствуют о большей эффективности дабигатрана в отношении снижения риска инсульта, внутричерепного кровоизлияния и смерти в сравнении с варфарином. Вместе с тем терапия дабигатраном чуть менее безопасна, чем лечение варфарином, и ассоциируется с увеличением риска большого желудочно-кишечного кровотечения.

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.

Хорошо известно, что самыми частыми и грозными осложнениями фибрилляции предсердий (ФП) являются системные тромбоэмболии (ТЭ) и в еще большей степени ишемические инсульты (ИИ). Известно также, что основным источником ТЭ являются тромбы в левом предсердии (ЛП), вернее, в ушке ЛП. Однако, говоря о длительном медикаментозном лечении ФП, мы подразумеваем в первую очередь терапию, ориентированную на контроль ритма и контроль частоты сердечных сокращений. И совершенно напрасно! Ведь больные умирают не от ФП, а от ее осложнений.

The article is a literature review on the problem of thromboembolic complications in non-valvular atrial fibrillation, the peculiarities of anticoagulant therapy and challenges associated with the selection of drugs for stroke prevention.

Высокая распространенность тромботических осложнений у пациентов с сердечно-сосудистыми заболеваниями обусловила широкое применение в клинической практике антикоагулянтной терапии. Длительное время основным антикоагулянтом, применяемым по этим показаниям, был препарат варфарин. При этом одними из наиболее распространенных осложнений были кровотечения, в т. ч. внутричерепные кровоизлияния. В последнее время все большее распространение получают новые оральные антикоагулянты (НОАК). Это определило необходимость сравнительной оценки их безопасности и эффективности с «классическим» антикоагулянтом варфарином, которая была проведена в ряде обширных клинических исследований этих лекарственных средств. Настоящий обзор посвящен анализу имеющихся данных о частоте внутричерепных кровоизлияний при применении антикоагулянтной терапии.

The article is a review of literature on the prognosis and prevention of stroke in patients with atrial fibrillation (AF). It is noted that the simple CHA2DS2-VASc calculator is a good predictor of the risk of stroke in AF. Oral anticoagulants are recommended to patients with one or more risk factors for stroke according to CHA2DS2-VASc. There is data from large randomized trials showing that new oral anticoagulants (dabigatran, rivaroxaban, apixaban) can be as good as or better than warfarin in significantly reducing the risk of stroke, and are associated with lower risk of serious, particularly intracranial, bleeding. Positive experience related to the use of dabigatran (Pradaxa®), in a dose of 150 mg or 110 mg twice in patients with AF, is described. The introduction of new anticoagulants into the national neurological practice which do not require international normalized ratio control, will ensure wider use of anticoagulant therapy in patients with AF and reduce the incidence of cardioembolic stroke.

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.