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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">russjcardiol</journal-id><journal-title-group><journal-title xml:lang="ru">Российский кардиологический журнал</journal-title><trans-title-group xml:lang="en"><trans-title>Russian Journal of Cardiology</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1560-4071</issn><issn pub-type="epub">2618-7620</issn><publisher><publisher-name>«SILICEA-POLIGRAF» LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.15829/1560-4071-2020-3921</article-id><article-id custom-type="elpub" pub-id-type="custom">russjcardiol-3921</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>КЛИНИКА И ФАРМАКОТЕРАПИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>GUIDELINES FOR THE PRACTITIONER</subject></subj-group></article-categories><title-group><article-title>Геморрагические осложнения терапии антикоагулянтами больных хронической сердечной недостаточностью в сочетании с хронической обструктивной болезнью легких и фибрилляцией предсердий. Опыт применения идаруцизумаба</article-title><trans-title-group xml:lang="en"><trans-title>Anticoagulant-related bleeding in patients with heart failure in combination with chronic obstructive pulmonary disease and atrial fibrillation. Experience with Idarucizumab</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0871-7551</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шпагина</surname><given-names>Л. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Shpagina</surname><given-names>L. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Шпагина Любовь Анатольевна — доктор медицинских наук, профессор, заведующий кафедрой госпитальной терапии и медицинской реабилитации; главный врач</p></bio><email xlink:type="simple">lashpagina@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0724-1539</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Котова</surname><given-names>О. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Kotova</surname><given-names>O. S.</given-names></name></name-alternatives><bio xml:lang="ru"/><bio xml:lang="en"><p>not</p></bio><email xlink:type="simple">ok526@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3109-9811</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шпагин</surname><given-names>И. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Shpagin</surname><given-names>I. S.</given-names></name></name-alternatives><bio xml:lang="ru"/><email xlink:type="simple">mkb-2@yandex.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7370-6958</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Локтин</surname><given-names>Е. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Loktin</surname><given-names>E. M.</given-names></name></name-alternatives><bio xml:lang="ru"/><email xlink:type="simple">mkb-2@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9342-4416</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Рукавицына</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Rukavitsyna</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"/><email xlink:type="simple">r-nastia@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Флягин</surname><given-names>Т. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Flyagin</surname><given-names>T. S.</given-names></name></name-alternatives><bio xml:lang="ru"/><bio xml:lang="en"><p>Novosibirsk</p></bio><email xlink:type="simple">mkb-2@yandex.ru</email><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Смарж</surname><given-names>Т. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Smarzh</surname><given-names>T. M.</given-names></name></name-alternatives><bio xml:lang="ru"/><bio xml:lang="en"><p>Novosibirsk</p></bio><email xlink:type="simple">mkb-2@yandex.ru</email><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3251-0315</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Камнева</surname><given-names>Н. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kamneva</surname><given-names>N. V.</given-names></name></name-alternatives><bio xml:lang="ru"/><email xlink:type="simple">mkb-2@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5694-2206</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Герасименко</surname><given-names>Д. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Gerasimenko</surname><given-names>D. A.</given-names></name></name-alternatives><bio xml:lang="ru"/><email xlink:type="simple">mkb-2@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6047-1707</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Аникина</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Anikina</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"/><email xlink:type="simple">mkb-2@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9176-0966</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Пономарева</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Ponomareva</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"/><email xlink:type="simple">mkb-2@yandex.ru</email><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБОУ ВО Новосибирский государственный медицинский университет Минздрава России; ГБУЗ Новосибирской области ГКБ № 2</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Novosibirsk State Medical University; City Clinical Hospital № 2</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГБОУ ВО Новосибирский государственный медицинский университет Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Novosibirsk State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>ГБУЗ Новосибирской области ГКБ 2</institution><country>Россия</country></aff><aff xml:lang="en"><institution>City Clinical Hospital № 2</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>ГБУЗ Новосибирской области ГКБ № 2</institution><country>Россия</country></aff><aff xml:lang="en"><institution>City Clinical Hospital № 2</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>07</day><month>06</month><year>2020</year></pub-date><volume>25</volume><issue>5</issue><fpage>3921</fpage><lpage>3921</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Шпагина Л.А., Котова О.С., Шпагин И.С., Локтин Е.М., Рукавицына А.А., Флягин Т.С., Смарж Т.М., Камнева Н.В., Герасименко Д.А., Аникина Е.В., Пономарева А.В., 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">Шпагина Л.А., Котова О.С., Шпагин И.С., Локтин Е.М., Рукавицына А.А., Флягин Т.С., Смарж Т.М., Камнева Н.В., Герасименко Д.А., Аникина Е.В., Пономарева А.В.</copyright-holder><copyright-holder xml:lang="en">Shpagina L.A., Kotova O.S., Shpagin I.S., Loktin E.M., Rukavitsyna A.A., Flyagin T.S., Smarzh T.M., Kamneva N.V., Gerasimenko D.A., Anikina E.V., Ponomareva A.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://russjcardiol.elpub.ru/jour/article/view/3921">https://russjcardiol.elpub.ru/jour/article/view/3921</self-uri><abstract><sec><title>Цель</title><p>Цель. Установить особенности кровотечений при терапии прямыми оральными антикоагулянтами больных хронической сердечной недостаточностью (СН) в сочетании с хронической обструктивной болезнью легких (ХОБЛ) и фибрилляцией предсердий. Показать эффективность идаруцизумаба в комплексной терапии тяжелого желудочного кровотечения, развившегося на фоне антикоагулянтной терапии дабигатраном.</p></sec><sec><title>Материал и методы</title><p>Материал и методы. В одноцентровое проспективное наблюдательное исследование включены 150 больных неклапанной фибрилляцией предсердий, получавших прямые оральные антикоагулянты, из них 75 с СН в сочетании с ХОБЛ (основная группа), 75 — с СН без коморбидности (группа сравнения). Группы сформированы методом подбора по индексу соответствия. Ковариа-тами для сопоставления были пол, возраст, риск кровотечения по HAS-BLED. Диагноз сердечной недостаточности соответствовал Федеральным клиническим рекомендациям, диагноз ХОБЛ — критериям GOLD 2011-2020. Оценивали частоту всех и больших кровотечений, кровотечений в жизненно-важные органы. Время наблюдения составило 14 (12; 16) мес. Для определения взаимосвязей применяли регрессионный анализ Кокса.</p></sec><sec><title>Результаты</title><p>Результаты. Частота больших кровотечений в течение года в группе СН и ХОБЛ была достоверно больше, отношение рисков (ОР) 3,0 (95% доверительный интервал (ДИ) 1,1-6,2), р=0,02 и не зависела от вида антикоагулянта. Гастроинтестинальные кровотечения составили 7 (9,3%) и 2 (2,7%) случая, ОР 3,5 (95% ДИ 1,1-7,3), р=0,05. У больных коморбидной патологией на риск больших и гастроинтестинальных кровотечений влияли: парциальное напряжение кислорода в артериальной крови, ОР 0,89 (95% ДИ 0,55-0,95) и ОР 0,88 (95% ДИ 0,50-0,98), соответственно, сывороточные концентрации NT-pro-BNP, ОР 1,10 (95% ДИ 1,05-2,14) и ОР 1,14 (95% ДИ 0,07-4,28), хемокин лиганда 18, ОР 1,15 (95% ДИ 1,11-5,75) и ОР 1,13 (95% ДИ 1,09-4,50). Представлен клинический случай применения идаруцизумаба для нейтрализации эффекта дабигатрана у больного с тяжелым кровотечением из эрозий пищевода, неклапанной фибрилляцией предсердий, СН и ХОБЛ. Нормокоагуляция была восстановлена в течение 4 ч, что позволило купировать кровотечение консервативными методами, способствовало успеху противошоковых мероприятий.</p></sec><sec><title>Заключение</title><p>Заключение. Антикоагулянтная терапия больных фибрилляцией предсердий при сердечной недостаточности в сочетании с ХОБЛ ассоциирована с дополнительным риском больших кровотечений, особенно, гастроинтестинальных. При выборе антикоагулянта следует учитывать возможность эффективного восстановления коагуляции в случае кровотечения.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Aim</title><p>Aim. To study the characteristics of direct oral anticoagulant-related bleeding in patients with heart failure in combination with chronic obstructive pulmonary disease (COPD) and atrial fibrillation. To show the efficacy of idarucizumab in complex therapy of severe gastrointestinal bleeding caused by dabigatran.</p></sec><sec><title>Material and methods</title><p>Material and methods. The single-center prospective observational study included 150 patients with nonvalvular atrial fibrillation treated with direct oral anticoagulants. Of these patients, 75 had heart failure in combination with COPD (experimental group) and 75 — HF without comorbidities (comparison group). Groups were formed by propensity score matching. Sex, age, bleeding risk by HAS-BLED score were covariates. HF was diagnosed in accordance with the criteria applied by Russian Federal clinical guidelines. COPD was diagnosed according to GOLD 2011-2020 criteria. Frequency of all bleeding, major bleeding, bleeding into critical organs were evaluated. Follow-up period was 14 (12; 16) months. Cox regression method was used to determine relationships.</p></sec><sec><title>Results</title><p>Results. Annual rate of major bleeding in group of HF and COPD was higher (Hazard ratio (HR) 3,0, 95% confidence interval (CI) 1,1-6,2, р=0,02), regardless of which anticoagulant was used. Gastrointestinal bleeding occurs in 7 (9,3%) and 2 (2,7%) patients (HR 3,5, 95% CI 1,1-7,3, р=0,05). In subjects with comorbidity, major and gastrointestinal bleeding were associated with partial pressure of arterial oxygen (HR 0,89, 95% CI 0,55-0,95 and HR 0,88, 95% CI 0,50-0,98 respectively), serum NT-pro-BNP (HR 1,10, 95% CI 1,05-2,14 and HR 1,14, 95% CI 0,07-4,28, respectively) and chemokine ligand 18 (HR 1,15, 95% CI 1,11-5,75 and HR 1,13, 95% CI 1,09-4,50). A case of successful use of idarucizumab for reversal of dabigatran anticoagulant effect in the patient with severe bleeding from esophageal erosion, nonvalvular AF, HF and COPD was reported. Coagulation was restored within 4 hours, which allowed to stop bleeding conservatively and antishock measures were effective.</p></sec><sec><title>Conclusion</title><p>Conclusion. Anticoagulation therapy in patients with AF and comorbidity of HF and COPD is associated with additional risk of major bleeding, especially gastrointestinal. Possibility to reverse the anticoagulant effect is an important argument when choosing an anticoagulant for these patients.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>прямые оральные антикоагулянты</kwd><kwd>кровотечения</kwd><kwd>идару-цизумаб</kwd></kwd-group><kwd-group xml:lang="en"><kwd>direct oral anticoagulants</kwd><kwd>bleeding</kwd><kwd>idarucizumab</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007 Jun 19;146(12):857-67. doi:10.7326/0003-4819-146-12-200706190-00007.</mixed-citation><mixed-citation xml:lang="en">Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. 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