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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="en"><front><journal-meta><journal-id journal-id-type="publisher-id">rpcardio</journal-id><journal-title-group><journal-title xml:lang="en">Rational Pharmacotherapy in Cardiology</journal-title><trans-title-group xml:lang="ru"><trans-title>Рациональная Фармакотерапия в Кардиологии</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1819-6446</issn><issn pub-type="epub">2225-3653</issn><publisher><publisher-name>«SILICEA-POLIGRAF» LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.20996/1819-6446-2019-15-5-697-705</article-id><article-id custom-type="elpub" pub-id-type="custom">rpcardio-2041</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="en"><subject>PREVENTIVE CARDIOLOGY AND PUBLIC HEALTH</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ПРОФИЛАКТИЧЕСКАЯ КАРДИОЛОГИЯ И ОБЩЕСТВЕННОЕ ЗДОРОВЬЕ</subject></subj-group></article-categories><title-group><article-title>Prediction of the Possibility of Hemorrhagic Syndrome during Combined Antiplatelet Therapy According to the Krasnodar Region Registry</article-title><trans-title-group xml:lang="ru"><trans-title>Прогнозирование возможности развития геморрагического синдрома на фоне комбинированной антитромбоцитарной терапии по данным регистра Краснодарского края</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Татаринцева</surname><given-names>З. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Tatarintseva</surname><given-names>Z. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>врач-кардиолог, зав. кардиологическим отделением №4, </p><p>350029, Краснодар, ул. 1 Мая, 167</p></bio><bio xml:lang="en"><p>MD, Cardiologist, Head of Cardiology Department №4,</p><p>Pervogo Maya ul. 167, Krasnodar, 350029</p></bio><email xlink:type="simple">tatarintsev_m@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>Космачева</surname><given-names>Е. Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Kosmacheva</surname><given-names>E. D.</given-names></name></name-alternatives><bio xml:lang="ru"><p>зам. главного врача по лечебной части, 350029, Краснодар, ул. 1 Мая, 167;</p><p>д.м.н., профессор, зав. кафедрой терапии №1, 350063, Краснодар, ул. Седина, 4</p></bio><bio xml:lang="en"><p>Deputy Chief Physician, Pervogo Maya ul. 167, Krasnodar, 350029;</p><p>MD, PhD, Professor, Head of Chair of Therapy №1, Sedina ul. 4, Krasnodar, 350063</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кручинова</surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kruchinova</surname><given-names>S. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>врач-кардиолог, 350029, Краснодар, ул. 1 Мая, 167;</p><p>аспирант, кафедра терапии №1, 350063, Краснодар, ул. Седина, 4</p></bio><bio xml:lang="en"><p>Cardiologist, Pervogo Maya ul. 167, Krasnodar, 350029;</p><p>MD, Postgraduate Student, Chair of Therapy №1, Sedina ul. 4, Krasnodar, 350063</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Акиньшина</surname><given-names>В. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Akinshina</surname><given-names>V. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.п.н., доцент, кафедра прикладной математики, </p><p>350063, Краснодар, ул. Седина, 4</p><p> </p></bio><bio xml:lang="en"><p>PhD (Pedagogics), Associate Professor, Chair of Applied Mathematics, </p><p>Sedina ul. 4, Krasnodar, 350063</p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Халафян</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Khalafyan</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д.т.н., профессор, кафедра прикладной математики, </p><p>350063, Краснодар, ул. Седина, 4</p></bio><bio xml:lang="en"><p>PhD (Technical), Professor, Chair of Applied Mathematics,</p><p>Sedina ul. 4, Krasnodar, 350063</p></bio><xref ref-type="aff" rid="aff-3"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Научно-исследовательский институт – Краевая клиническая больница №1 им. проф. С.В. Очаповского</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Research Institute – Ochapovsky Regional Clinical Hospital №1</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Научно-исследовательский институт – Краевая клиническая больница №1 им. проф. С.В. Очаповского;&#13;
Кубанский государственный медицинский университет</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Research Institute – Ochapovsky Regional Clinical Hospital №1;&#13;
Kuban State University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>Кубанский государственный медицинский университет</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Kuban State University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>05</day><month>11</month><year>2019</year></pub-date><volume>15</volume><issue>5</issue><fpage>697</fpage><lpage>705</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Tatarintseva Z.G., Kosmacheva E.D., Kruchinova S.V., Akinshina V.A., Khalafyan A.A., 2019</copyright-statement><copyright-year>2019</copyright-year><copyright-holder xml:lang="ru">Татаринцева З.Г., Космачева Е.Д., Кручинова С.В., Акиньшина В.А., Халафян А.А.</copyright-holder><copyright-holder xml:lang="en">Tatarintseva Z.G., Kosmacheva E.D., Kruchinova S.V., Akinshina V.A., Khalafyan A.A.</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://www.rpcardio.online/jour/article/view/2041">https://www.rpcardio.online/jour/article/view/2041</self-uri><abstract><sec><title>Background</title><p>Background. According to the literature data, acute coronary syndrome (ACS) in 2-20 % of cases is combined with atrial fibrillation (AF). According to the current guidelines of the European Society of Cardiology (ESC), patients with coexisting AF and ACS should receive dual antiplatelet therapy for the prevention of recurrent cardiovascular events and anticoagulant therapy for the prevention of thromboembolic complications. However, this combination is fraught with the development of hemorrhagic syndrome.</p></sec><sec><title>Aim</title><p>Aim. To develop a model and software module for predicting possible bleeding in patients with ACS combined with AF taking three-component antithrombotic therapy.</p></sec><sec><title>Materials and Methods</title><p>Materials and Methods. To build prognostic models for the development of hemorrhagic syndrome, a statistical method was used for classification trees and the neural network procedure implemented in the STATISTICA package. To build prognostic models, a sample was used consisting of 201 patients with a combination of ACS and AF with and without fatal outcome, the state of which was described by 42 quantitative and qualitative clinical indicators. The control group included 205 patients with ACS and intact sinus rhythm.</p></sec><sec><title>Results</title><p>Results. To identify predictors of predictive models of the possible development of hemorrhagic syndrome in patients with triple antithrombotic therapy, the Spearman correlation coefficient was used. The study of correlations allowed to reveal clinical indicators – predictors of prognostic models. After analyzing the predictive ability of the developed models, a software module was created in the Microsoft Visual C # 2015 programming environment that allows determining the possibility of hemorrhagic syndrome in patients with a combination of ACS and AF using classification trees and neural networks.</p></sec><sec><title>Сonclusion</title><p>Сonclusion. A classification model and a software module were developed to predict possible bleeding in patients taking three-component antithrombotic therapy. Models contain both quantitative and qualitative (categorical) clinical indicators. The current level of development of data analysis technologies opens up broad horizons for medicine in solving problems on real medical data, without translating them into scoring risk scales, including prediction of the diagnosis of the disease, stage of the disease, treatment outcome, possible complications, etc. High reliability of such systems can be provided by large volumes of medical data accumulated on servers. </p></sec></abstract><trans-abstract xml:lang="ru"><p>По данным литературы острый коронарный синдром (ОКС) в 2-20% случаев сочетается с фибрилляцией предсердий (ФП). Согласно настоящему руководству Европейского общества кардиологии (ESC) пациенты с ФП и ОКС должны получать двойную антиагрегантную терапию с целью профилактики повторных сердечно-сосудистых событий и антикоагулянтную терапию с целью профилактики тромбоэмболических осложнений. Однако такое сочетание чревато развитием геморрагического синдрома.</p><sec><title>Цель</title><p>Цель. Разработать модель и программный модуль для прогнозирования возможных кровотечений у больных ОКС в сочетании с ФП, принимающих трехкомпонентную антитромботическую терапию.</p></sec><sec><title>Материал и методы</title><p>Материал и методы. Для построения прогностических моделей возможности развития геморрагического синдрома были использованы статистический метод «деревья классификации» и процедура «нейронные сети», реализованные в пакете STATISTICA. Для построения прогностических моделей была использована выборка из 201 больного с сочетанием ОКС и ФП с летальным исходом и без него, состояние которых описывалось по 42 количественным и качественным клиническим показателям. В контрольную группу включены 205 пациентов с ОКС и сохранным синусовым ритмом.</p></sec><sec><title>Результаты</title><p>Результаты. Для выявления предикторов моделей прогнозирования возможного развития геморрагического синдрома у пациентов с тройной антитромботической терапией использовали коэффициент корреляции Спирмена. Исследование корреляции позволило выявить клинические показатели – предикторы прогностических моделей. После анализа прогностической способности разработанных моделей в среде программирования Microsoft Visual C# 2015 был создан программный модуль, позволяющий определить возможность геморрагического синдрома у пациентов с сочетанием ОКС и ФП с помощью деревьев классификации и нейронных сетей.</p></sec><sec><title>Заключение</title><p>Заключение. Была разработана классификационная модель и программный модуль для прогнозирования возможных кровотечений у больных, принимающих трехкомпонентную антитромботическую терапию. Модели содержат как количественные клинические показатели, так и качественные (категориальные). Уровень развития современных технологий анализа данных открывает для медицины широкие горизонты по решению задач на реальных медицинских данных, не переводя их в балльные шкалы риска, и включающий прогнозирование диагноза заболевания, стадии заболевания, исхода лечения, возможных осложнений и т.д. Высокая достоверность таких систем может быть обеспечена большими объемами накопленных на серверах медицинских данных. </p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>острый коронарный синдром</kwd><kwd>фибрилляция предсердий</kwd><kwd>регистр</kwd><kwd>прогнозирование геморрагического синдрома</kwd></kwd-group><kwd-group xml:lang="en"><kwd>acute coronary syndrome</kwd><kwd>atrial fibrillation</kwd><kwd>register</kwd><kwd>prognosis of hemorrhagic syndrome</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">Jabre P., Roger V.L., Murad M.H., et al. Mortality associated with atrial fibrillation in patients with myocardial infarction: a systematic review and meta-analysis. Circulation. 2011;123:1587-93. DOI:10.1161/CIRCULATIONAHA.110.986661.</mixed-citation><mixed-citation xml:lang="en">Jabre P., Roger V.L., Murad M.H., et al. Mortality associated with atrial fibrillation in patients with myocardial infarction: a systematic review and meta-analysis. Circulation. 2011;123:1587-93. DOI:10.1161/CIRCULATIONAHA.110.986661.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">ACC/AHA Task Force Members. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014;130:199-267. DOI: 10.1161/CIR.0000000000000041.</mixed-citation><mixed-citation xml:lang="en">ACC/AHA Task Force Members. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014;130:199-267. DOI: 10.1161/CIR.0000000000000041.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Hansen M.L., Sorensen R., Clausen M.T., et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med. 2010;170:1433- 41. DOI:10.1001/archinternmed.2010.271.</mixed-citation><mixed-citation xml:lang="en">Hansen M.L., Sorensen R., Clausen M.T., et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med. 2010;170:1433- 41. DOI:10.1001/archinternmed.2010.271.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Persson J., Lindbaeck J., Hofman-Bang C., et al. Efficacy and safety of clopidogrel after PCI with stenting in patients on oral anticoagulants with acute coronary syndrome. Euro Intervention. 2011;6:1046- 52. DOI:10.4244/EIJV6I9A183.</mixed-citation><mixed-citation xml:lang="en">Persson J., Lindbaeck J., Hofman-Bang C., et al. Efficacy and safety of clopidogrel after PCI with stenting in patients on oral anticoagulants with acute coronary syndrome. Euro Intervention. 2011;6:1046- 52. DOI:10.4244/EIJV6I9A183.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Guasch E., Sionis A., Reverter J.C., et al. Safety issues of adjunctive clopidogrel in patients discharged after percutaneous coronary intervention with stent placement and requiring oral anticoagulation. Int J Cardiol. 2011;146:e1-e4. DOI:10.1016/j.ijcard.2008.12.170.</mixed-citation><mixed-citation xml:lang="en">Guasch E., Sionis A., Reverter J.C., et al. Safety issues of adjunctive clopidogrel in patients discharged after percutaneous coronary intervention with stent placement and requiring oral anticoagulation. Int J Cardiol. 2011;146:e1-e4. DOI:10.1016/j.ijcard.2008.12.170.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Gao F., Zhou Y.J., Wang Z.J., et al. Comparison of Different Antithrombotic Regimens for Patients with Atrial Fibrillation Undergoing Drug-Eluting Stent Implantation. Circ J. 2010;74:701-8. DOI:10.1253/circj.CJ-09-0880.</mixed-citation><mixed-citation xml:lang="en">Gao F., Zhou Y.J., Wang Z.J., et al. Comparison of Different Antithrombotic Regimens for Patients with Atrial Fibrillation Undergoing Drug-Eluting Stent Implantation. Circ J. 2010;74:701-8. DOI:10.1253/circj.CJ-09-0880.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Zhao H.J., Zheng Z.T., Wang Z.H., et al. “Triple Therapy” Rather Than “Triple Threat” A Meta-analysis of the Two Antithrombotic Regimens After Stent Implantation in Patients Receiving Long-term Oral Anticoagulant Treatment. Chest. 2011;139(2):260-70. DOI:10.1378/chest.09-3083.</mixed-citation><mixed-citation xml:lang="en">Zhao H.J., Zheng Z.T., Wang Z.H., et al. “Triple Therapy” Rather Than “Triple Threat” A Meta-analysis of the Two Antithrombotic Regimens After Stent Implantation in Patients Receiving Long-term Oral Anticoagulant Treatment. Chest. 2011;139(2):260-70. DOI:10.1378/chest.09-3083.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Maegdefessel L., Schlitt A., Faerber J., et al. Anticoagulant and/or antiplatelet treatment in patients with atrial fibrillation after percutaneous coronary intervention. A single-center experience. Med Klin (Munich). 2008;103(9):628-32. DOI:10.1007/s00063-008-1101-4.</mixed-citation><mixed-citation xml:lang="en">Maegdefessel L., Schlitt A., Faerber J., et al. Anticoagulant and/or antiplatelet treatment in patients with atrial fibrillation after percutaneous coronary intervention. A single-center experience. Med Klin (Munich). 2008;103(9):628-32. DOI:10.1007/s00063-008-1101-4.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Rubboli A., Halperin J.L. Antithrombotic therapy with warfarin, aspirin and clopidogrel is the recommended regime in anticoagulated patients who present with an acute coronary syndrome and/or undergo percutaneous coronary interventions. Thromb Haemost. 2008;100(5):752-3.</mixed-citation><mixed-citation xml:lang="en">Rubboli A., Halperin J.L. Antithrombotic therapy with warfarin, aspirin and clopidogrel is the recommended regime in anticoagulated patients who present with an acute coronary syndrome and/or undergo percutaneous coronary interventions. Thromb Haemost. 2008;100(5):752-3.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">DeEugenio D., Kolman L., DeCaro M., et al. Risk of major bleeding with concomitant dual antiplatelet therapy after percutaneous coronary intervention in patients receiving long-term warfarin therapy. Pharmacoherapy. 2007;27(5):691-6. DOI:10.1592/phco.27.5.691.</mixed-citation><mixed-citation xml:lang="en">DeEugenio D., Kolman L., DeCaro M., et al. Risk of major bleeding with concomitant dual antiplatelet therapy after percutaneous coronary intervention in patients receiving long-term warfarin therapy. Pharmacoherapy. 2007;27(5):691-6. DOI:10.1592/phco.27.5.691.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Rubboli A., Colletta M., Herzfeld J., et al. Peri-procedural and medium-term antithrombotic strategies in patients with an indication for long-term anticoagulation undergoing coronary angiography and intervention. Coron Artery Dis. 2007;18:193-9. DOI:10.1097/MCA.0b013e328012a964.</mixed-citation><mixed-citation xml:lang="en">Rubboli A., Colletta M., Herzfeld J., et al. Peri-procedural and medium-term antithrombotic strategies in patients with an indication for long-term anticoagulation undergoing coronary angiography and intervention. Coron Artery Dis. 2007;18:193-9. DOI:10.1097/MCA.0b013e328012a964.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Authors/Task Force Members, Camm A.J., Lip G.Y., De Caterina R., et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: An update of the 2010 ESC Guidelines for the management of atrial fibrillation Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33(21):2719-47. DOI:10.1093/eurheartj/ehs253.</mixed-citation><mixed-citation xml:lang="en">Authors/Task Force Members, Camm A.J., Lip G.Y., De Caterina R., et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: An update of the 2010 ESC Guidelines for the management of atrial fibrillation Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33(21):2719-47. DOI:10.1093/eurheartj/ehs253.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Pisters R., Lane D.A., Nieuwlaat R., et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093-100. DOI:10.1378/chest.10-0134.</mixed-citation><mixed-citation xml:lang="en">Pisters R., Lane D.A., Nieuwlaat R., et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093-100. DOI:10.1378/chest.10-0134.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Халафян А.А. STATISTICA 6. Математическая статистика с элементами теории вероятностей. М.: Бином; 2010.</mixed-citation><mixed-citation xml:lang="en">Khalafyan A.A. STATISTICA 6. Mathematical statistics with elements of probability theory. Moscow: Binom; 2010 (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Боровиков В.П., ред. Нейронные сети STATISTICA Neural Networks. Методология и технологии современного анализа данных: учебное пособие. 2-e изд. М.: Горячая линия – Телеком; 2008</mixed-citation><mixed-citation xml:lang="en">Borovikov V.P., ed. Neural networks STATISTICA Neural Networks. Methodology and technologies of modern data analysis: a textbook (2nd ed.). Moscow: Hot Line - Telecom; 2008 (In Russ.)</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
