medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2021-14-68-76medsovet-6428Research ArticleАНТИТРОМБОТИЧЕСКАЯ ТЕРАПИЯANTITHROMBOTIC THERAPYСистематические ошибки в выборе дозы прямых пероральных антикоагулянтов: актуальность проблемы и подходы к ее решениюSystematic errors in the choice of dose level of direct oral anticoagulants: urgency of an issue and approaches to its solutionhttps://orcid.org/0000-0002-8505-1848ГиляревскийС. Р.GilyarevskiyS. R.

Гиляревский Сергей Руджерович, д.м.н., профессор кафедры клинической фармакологии и терапии

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Sergey R. Gilyarevskiy, Dr. Sci. (Med.), Professor of the Department of Clinical Pharmacology and Therapy

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

sgilarevsky@rambler.ruhttps://orcid.org/0000-0003-3102-1958БенделианиН. Г.BendelianiN. G.

Бенделиани Нана Георгиевна, д.м.н., старший научный сотрудник научно- консультативного отделения 

119049, Москва, Ленинский проспект, д. 8, корп. 4

Nana G. Bendeliani, Dr. Sci. (Med.), Senior Research Associate, Scientific Advisory Department

8, Bldg. 4, Leninskiy Ave., Moscow, 119049

n.bendo@mail.ruhttps://orcid.org/0000-0002-9865-4998ГолшмидМ. В.GolshmidM. V.

Голшмид Мария Владимировна, к.м.н., доцент кафедры клинической фармакологии и терапии

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Maria V. Golshmid, Cand. Sci. (Med.), Associate Professor of the Department of Clinical Pharmacology and Therapy

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

golshmid@yandex.ruhttps://orcid.org/0000-0001-9458-7305КузьминаИ. М.KuzminaI. M.

Кузьмина Ирина Михайловна, к.м.н., заведующая научным отделением неотложной кардиологии

129090, Москва, Б. Сухаревская пл., д. 3, стр. 21

Irina M. Kuzmina, Cand. Sci. (Med.), Head of Research Department of Emergency Cardiology

3, Bldg. 21, B. Sukharevskaya Square, Moscow, 129090

kuzmina.sklif@gmail.comРоссийская медицинская академия непрерывного профессионального образованияРоссияRussian Medical Academy of Continuing Postgraduate EducationRussian FederationИнститут коронарной и сосудистой хирургии Национального медицинского исследовательского центра сердечнососудистой хирургии имени А.Н. БакулеваРоссияInstitute for Coronary and Vascular Surgery of A.N. Bakulev National Medical Research Center of Cardiovascular SurgeryRussian FederationНаучно-исследовательский институт скорой помощи имени Н.В. СклифосовскогоРоссияSklifosovskiy Research Institute for Emergency MedicineRussian Federation2021171020210146876Copyright © Гиляревский С.Р., Бенделиани Н.Г., Голшмид М.В., Кузьмина И.М., 20212021Гиляревский С.Р., Бенделиани Н.Г., Голшмид М.В., Кузьмина И.М.Gilyarevskiy S.R., Bendeliani N.G., Golshmid M.V., Kuzmina I.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/6428

В статье представлены современные данные о частоте применения прямых пероральных антикоагулянтов (дабигатрана, ривароксабана, апиксабана и эдоксабана) в нерекомендуемых низких дозах. Дается обоснование актуальности проблемы обеспечения максимальной эффективности применения антикоагулянтов в клинической практике с учетом высокой распространенности фибрилляции предсердий и  фармакологических характеристик наиболее часто применяемых препаратов. Обсуждаются последствия такого необоснованного снижения доз антикоагулянтов у пациентов пожилого и старческого возраста. Приводятся результаты недавно выполненных обсервационных исследований, в ходе выполнения которых оценивалась связь между применением прямых пероральных антикоагулянтов и риском развития неблагоприятных клинических исходов. Обсуждаются данные о связи между применением необоснованно сниженных доз антикоагулянтов у пациентов с фибрилляцией предсердий, которые недавно были получены в ходе выполнения регистра GARFIELD-AF. Приводятся данные о достаточно высокой вариабельности концентрации прямых пероральных антикоагулянтов. Особое место в статье уделяется частоте применения апиксабана в  необоснованно сниженной дозе, а  также последствиям использования нерекомендуемых доз апиксабана. Подчеркивается необоснованность попыток дополнительного снижения риска развития кровотечений за  счет необоснованного снижения доз апиксабана, учитывая устойчивые данные о высокой безопасности применения апиксабана в рекомендуемых дозах, а также возможном снижении эффекта при нерекомендуемом снижении его дозы. Приведены данные о критериях снижения доз, которые приняты в разных странах. Обсуждаются предлагаемые термины для обозначения разных доз прямых пероральных антикоагулянтов в зависимости от их изученности в ходе выполнения крупных рандомизированных исследований.

The article presents updated information on the frequency of use of non-recommended low dosing of direct oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban). It gives substantiation of the urgency of the issue of providing the maximum efficiency of the use of anticoagulants in clinical practice, taking into account the high prevalence of atrial fibrillation and the pharmacological characteristics of the most commonly used drugs. The effects of such an unreasonable reduction in anticoagulant doses in elderly and senile patients are discussed. The results of recent observational studies that assessed the relationship between the use of direct oral anticoagulants and the risk of adverse clinical outcomes are presented. The data on the relationship between the use of unreasonably low dosing of anticoagulants in patients with atrial fibrillation, which were recently obtained during the implementation of the GARFIELD-AF registry, are discussed. The data on a rather high variability of concentrations of direct oral anticoagulants are presented. The frequency of using apixaban in an unreasonably reduced dose, as well as the effects of using non-recommended doses of apixaban hold a specific place in the article. The unreasonableness of attempts to further reduce the risk of bleeding due to unreasonable reduction of apixaban dosing is emphasized, taking into account the stable data on the high safety of recommended dosing of apixaban, as well as the possible decrease in the effect if the dose reduction is not recommended. The data on the criteria for dose reduction, which are adopted in different countries, are presented. The proposed terms to designate different doses of direct oral anticoagulants, depending on their study in the course of large, randomized trials are discussed.

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The authors declare that there are no conflicts of interest present.