<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<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">10.20996/1819-6446-2019-15-5-663-669</article-id><article-id custom-type="elpub" pub-id-type="custom">rpcardio-2036</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>NOTES FROM PRACTICE</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>КЛИНИЧЕСКИЙ ОПЫТ</subject></subj-group></article-categories><title-group><article-title>Possibilities of Combination of Beta-blockers and Ivabradine in Patients with Stable Angina Pectoris</article-title><trans-title-group xml:lang="ru"><trans-title>Возможности применения комбинации бета-адреноблокаторов и ивабрадина у пациентов со стабильной стенокардией</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>Кашталап</surname><given-names>В. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kashtalap</surname><given-names>V. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д.м.н., зав. лабораторией патофизиологии мультифокального атеросклероза, 650002, Кемерово, Сосновый б-р, 6;</p><p>доцент, кафедра кардиологии и сердечно-сосудистой хирургии, 650029, Кемерово, ул. Ворошилова, 22А</p></bio><bio xml:lang="en"><p>MD, PhD, Head of Laboratory of Pathophysiology of Multifocal Atherosclerosis, Sosnoviy bulv. 6, Kemerovo, 650002 </p><p>Associate Professor, Chair of Cardiology and Cardiovascular Surgery, Voroshilova ul. 22A, Kemerovo, 650029</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Барбараш</surname><given-names>О. Л.</given-names></name><name name-style="western" xml:lang="en"><surname>Barbarash</surname><given-names>O. L.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д.м.н., профессор, чл.корр. РАН, директор НИИ, 650002, Кемерово, Сосновый б-р, 6;</p><p>зав. кафедрой кардиологии и сердечно-сосудистой хирургии, , 650029, Кемерово, ул. Ворошилова, 22А</p></bio><bio xml:lang="en"><p>MD, PhD, Corresponding Member of the Russian Academy of Sciences, Director, Sosnoviy bulv. 6, Kemerovo, 650002;</p><p>Head of Chair of Cardiology and Cardiovascular Surgery, Voroshilova ul. 22A, Kemerovo, 650029</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>Седых</surname><given-names>Д. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Sedykh</surname><given-names>D. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.м.н., н.с., лаборатория патофизиологии мультифокального атеросклероза;</p><p>врач-кардиолог,</p><p>650002, Кемерово, Сосновый б-р, 6</p></bio><bio xml:lang="en"><p>MD, PhD, Researcher, Laboratory of Pathophysiology of Multifocal Atherosclerosis, Sosnoviy bulv. 6, Kemerovo, 650002; </p><p>Cardiologist, Voroshilova ul. 22A, Kemerovo, 650029 </p></bio><email xlink:type="simple">md-sedih@mail.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>Кривошапова</surname><given-names>К. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Krivoshapova</surname><given-names>K. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.м.н., н.с., лаборатория патофизиологии мультифокального атеросклероза,;</p><p>врач-кардиолог, </p><p>650002, Кемерово, Сосновый б-р, 6</p></bio><bio xml:lang="en"><p>MD, PhD, Researcher, Laboratory of Pathophysiology of Multifocal Atherosclerosis, Sosnoviy bulv. 6, Kemerovo, 650002;</p><p>Cardiologist, Voroshilova ul. 22A, Kemerovo, 650029 </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>Цыганкова</surname><given-names>Д. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Tsygankova</surname><given-names>D. P.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.м.н., н.с., лаборатория эпидемиологии сердечно-сосудистых заболеваний;</p><p>врач-эндокринолог, </p><p>650002, Кемерово, Сосновый б-р, 6</p></bio><bio xml:lang="en"><p>MD, PhD, Researcher, Laboratory of Cardiovascular Diseases Epidemiology, Sosnoviy bulv. 6, Kemerovo, 650002;</p><p>Endocrinologist, Voroshilova ul. 22A, Kemerovo, 650029 </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>Цыганкова</surname><given-names>О. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Tsygankova</surname><given-names>O. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д.м.н., профессор, кафедра неотложной терапии с эндокринологией и профпатологией, </p><p>630091, Новосибирск, Красный просп., 52</p></bio><bio xml:lang="en"><p>MD, PhD, Professor, Chair of Emergency Therapy with Endocrinology and Occupational Pathology,</p><p>Krasniy prosp. 52, Novosibirsk, 630091</p></bio><xref ref-type="aff" rid="aff-4"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний;&#13;
Кемеровский государственный медицинский университет</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Research Institute for Complex Issues of Cardiovascular Diseases;&#13;
Kemerovo State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний;&#13;
Кемеровский государственный медицинский университет</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Research Institute for Complex Issues of Cardiovascular Diseases; &#13;
Kemerovo State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний;&#13;
Кемеровский областной клинический кардиологический диспансер</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Research Institute for Complex Issues of Cardiovascular Diseases;&#13;
Kemerovo State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>Новосибирский государственный медицинский университет</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Novosibirsk State Medical 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>04</day><month>11</month><year>2019</year></pub-date><volume>15</volume><issue>5</issue><fpage>663</fpage><lpage>669</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Kashtalap V.V., Barbarash O.L., Sedykh D.Y., Krivoshapova K.E., Tsygankova D.P., Tsygankova O.V., 2019</copyright-statement><copyright-year>2019</copyright-year><copyright-holder xml:lang="ru">Кашталап В.В., Барбараш О.Л., Седых Д.Ю., Кривошапова К.Е., Цыганкова Д.П., Цыганкова О.В.</copyright-holder><copyright-holder xml:lang="en">Kashtalap V.V., Barbarash O.L., Sedykh D.Y., Krivoshapova K.E., Tsygankova D.P., Tsygankova O.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://www.rpcardio.online/jour/article/view/2036">https://www.rpcardio.online/jour/article/view/2036</self-uri><abstract><sec><title>Aim</title><p>Aim. To evaluate the therapeutic efficacy of a combination of ivabradine and beta-blockers (BAB) in patients with stable angina, initially taking only BAB and not reaching the target heart rate (HR) due to the risk of hypotension.</p></sec><sec><title>Material and methods</title><p>Material and methods. A prospective observational post-registration study was performed at the Research Institute for Complex Issues of Cardiovascular Diseases. The study included 50 patients with stable angina pectoris (diagnosed by coronary angiography in combination with clinical manifestations of angina of functional class II-III according to the Canadian classification) and an initial sinus rhythm with a heart rate of more than 70 beats per minute. These patients have already taken BAB. Heart rate, the number of angina attacks, nitrate intake and quality of life indicators according to the questionnaire were evaluated as criteria for therapeutic efficacy.</p></sec><sec><title>Results</title><p>Results. Taking the study drug in combination with BAB led to a significant decrease the average heart rate at rest by 20%, as well as after a six-minute walk test (TLC) in most patients (p&lt;0.050), and a decrease in the total number of angina attacks per week from 5 to less than 1 (p&lt;0.050) and the frequency of nitrate intake for the relief of angina attacks from 58% to 20% (p=0.001). Therapy with ivabradine (Bravadin) was well tolerated by patients: there were no adverse events in the observed sample of patients, patients had a high adherence to treatment (100% of the contents of handed out blisters were used). During the 3 months of follow-up, according to the EQ-5D-5L quality of life questionnaire, patients improved their perception of their own health level (p&lt;0.050), the number of patients experiencing mild (p=0.034) and strong (p=0.041) mobility limitations decreased; strong (p=0.024) restriction in self-care, mild (p=0.041) and strong (p=0.024) restriction of daily activities, mild manifestation of pain (p=0.009) and mild anxiety (p=0.027) also were reduced compared with the initial questionnaires.</p></sec><sec><title>Conclusion</title><p>Conclusion. Ivabradine (Bravadin) in addition to BAB is an effective and safe antianginal therapy for the prevention of angina attacks by reducing the initially high heart rate in patients with angina pectoris of functional class II-III.</p></sec></abstract><trans-abstract xml:lang="ru"><sec><title>Цель</title><p>Цель. Оценить терапевтическую эффективность комбинации ивабрадина и бета-адреноблокаторов (БАБ) у пациентов со стабильной стенокардией, исходно принимавших только БАБ и не достигших целевой частоты сердечных сокращений (ЧСС) из-за угрозы развития гипотонии.</p></sec><sec><title>Материал и методы</title><p>Материал и методы. Проспективное наблюдательное пострегистрационное исследование выполнено в НИИ КПССЗ. В работу были включены 50 пациентов со стабильной стенокардией (диагностированной по результатам коронарографии в сочетании с клиническими проявлениями стенокардии напряжения II-III функционального классов по Канадской классификации) на фоне приема БАБ при исходно синусовом ритме с ЧСС более 70 уд/мин. В качестве критериев терапевтической эффективности оценивались ЧСС, количество приступов стенокардии, потребление нитратов и показатели качества жизни согласно опроснику.</p></sec><sec><title>Результаты</title><p>Результаты. Прием исследуемого лекарственного препарата в сочетании с БАБ привел к достоверному снижению средней ЧСС в покое на 20%, а также после теста 6-ти минутной ходьбы у большинства пациентов (р&lt;0,050), снижению общего числа приступов стенокардии за неделю с 5 до менее 1 (р&lt;0,050) и частоты приема нитратов для купирования приступов стенокардии с 58% до 20% (р=0,001). Терапия ивабрадином (Бравадином) хорошо переносилась пациентами: нежелательные явления в наблюдаемой выборке больных отсутствовали, пациенты имели высокую приверженность к лечению (на 100% использовано содержимое блистеров препарата, выданного на руки). В течение 3 мес наблюдения у пациентов согласно данным опросника качества жизни EQ-5D-5L улучшилось восприятие уровня собственного здоровья (р&lt;0,050), уменьшилось количество пациентов, испытывающих легкое (р=0,034) и сильное (р=0,041) ограничение в подвижности; сильное (р=0,024) ограничение в самообслуживании, легкое (р=0,041) и сильное (р=0,024) ограничение повседневной деятельности, легкое проявление болевого синдрома (р=0,009) и легкую тревожность (р=0,027) по сравнению с данными исходного анкетирования.</p></sec><sec><title>Заключение</title><p>Заключение. Назначение ивабрадина (Бравадина) в дополнение к БАБ является эффективной и безопасной антиангинальной терапией для профилактики приступов стенокардии за счет снижения исходно высокой ЧСС у пациентов со стенокардией II-III функционального классов. </p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>антиангинальная терапия</kwd><kwd>ивабрадин</kwd><kwd>стабильная стенокардия</kwd><kwd>эффективность</kwd><kwd>безопасность</kwd><kwd>качество жизни</kwd></kwd-group><kwd-group xml:lang="en"><kwd>antianginal therapy</kwd><kwd>ivabradine</kwd><kwd>stable angina pectoris</kwd><kwd>efficacy</kwd><kwd>safety</kwd><kwd>quality of life</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">Members Task Force Members; Montalescot G., Sechtem U., Achenbach S., et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013;34(38):2949-3003. DOI:10.1093/eurheartj/eht296.</mixed-citation><mixed-citation xml:lang="en">Members Task Force Members; Montalescot G., Sechtem U., Achenbach S., et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013;34(38):2949-3003. DOI:10.1093/eurheartj/eht296.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Стабильная ишемическая болезнь сердца. Клинические рекомендации (2016). (Цитировано 15.04.2019) Доступно на: http://cr.rosminzdrav.ru/schema.html?id=133#/text.</mixed-citation><mixed-citation xml:lang="en">Stable ischemic heart disease. Clinical recommendations (2016) [cited by Apr 15, 2019]. Available from: http://cr.rosminzdrav.ru/schema.html?id=133#/text (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Di Francesco D. Funny channels in the control of cardiac rhythm and mode of action of selective blockers. Pharmacol Res. 2006;53:399-406. DOI:10.1016/j.phrs.2006.03.006.</mixed-citation><mixed-citation xml:lang="en">Di Francesco D. Funny channels in the control of cardiac rhythm and mode of action of selective blockers. Pharmacol Res. 2006;53:399-406. DOI:10.1016/j.phrs.2006.03.006.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Суджаева О.А. Различные подходы к оптимальной медикаментозной терапии стабильной стенокардии с использованием ивабрадина (кораксан). Медицинские Новости. 2016;5:17-22.</mixed-citation><mixed-citation xml:lang="en">Sudgaeva O.A. Various approaches to the optimal medical therapy of stable angina with the use of ivabradine (coraxan). Медицинские Новости. 2016;5:17-22. (In Russ).</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Поветкин С.В., Лунева Ю.В. Изучение клинической эффективности оригинального и дженерического препаратов ивабрадина у пациентов со стабильной стенокардией напряжения (сравнительное исследование). Рациональная Фармакотерапия в Кардиологии. 2018;14(1):34-39. DOI: 10.20996/1819-6446-2018-14-1-34-39.</mixed-citation><mixed-citation xml:lang="en">Povetkin S.V., Luneva J.V. Study of Clinical Efficacy of Original and Generic Drugs of Ivabradine in Patients with Stable Angina (Сomparative Study). Rational Pharmacotherapy in Cardiology 2018;14(1):34-39. DOI: 10.20996/1819-6446-2018-14-1-34-39 (In Russ).</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Tardif J.C., Ponikowski P., Kahan T. Efficacy of the I(f) current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4-month, randomized, placebo-controlled trial. Eur Heart J. 2009;30:540-8. DOI:10.1093/eurheartj/ehn571.</mixed-citation><mixed-citation xml:lang="en">Tardif J.C., Ponikowski P., Kahan T. Efficacy of the I(f) current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4-month, randomized, placebo-controlled trial. Eur Heart J. 2009;30:540-8. DOI:10.1093/eurheartj/ehn571.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Fox K., Ford I., Steg P.G., et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:807-16. DOI:10.1016/S0140-6736(08)61170-8.</mixed-citation><mixed-citation xml:lang="en">Fox K., Ford I., Steg P.G., et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:807-16. DOI:10.1016/S0140-6736(08)61170-8.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Fox K., Ford I., Steg P.G., et al. Relationship between ivabradine treatment and cardiovascular outcomes in patients with stable coronary artery disease and left ventricular systolic dysfunction with limiting angina: a subgroup analysis of the randomized, controlled BEAUTIFUL trial. Eur Heart J. 2009;30:2337-45. DOI:10.1093/eurheartj/ehp358.</mixed-citation><mixed-citation xml:lang="en">Fox K., Ford I., Steg P.G., et al. Relationship between ivabradine treatment and cardiovascular outcomes in patients with stable coronary artery disease and left ventricular systolic dysfunction with limiting angina: a subgroup analysis of the randomized, controlled BEAUTIFUL trial. Eur Heart J. 2009;30:2337-45. DOI:10.1093/eurheartj/ehp358.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Swedberg K., Komajda M., Bohm M., et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;376:875-85. DOI:10.1016/S0140-6736(10)61198-1.</mixed-citation><mixed-citation xml:lang="en">Swedberg K., Komajda M., Bohm M., et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;376:875-85. DOI:10.1016/S0140-6736(10)61198-1.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Bohm M., Swedberg K., Komajda M., et al. Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet. 2010;376:886-94. DOI:10.1016/S0140-6736(10)61259-7.</mixed-citation><mixed-citation xml:lang="en">Bohm M., Swedberg K., Komajda M., et al. Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet. 2010;376:886-94. DOI:10.1016/S0140-6736(10)61259-7.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Swedberg K., Komajda M., Bohm M., et al. Effects on outcomes of heart rate reduction by ivabradine in patients with congestive heart failure: is there an influence of beta-blocker dose? Findings from the SHIFT (Systolic Heart failure treatment with the I(f ) inhibitor ivabradine Trial) study. J Am Coll Cardiol. 2012;59:1938-45. DOI:10.1016/j.jacc.2012.01.020.</mixed-citation><mixed-citation xml:lang="en">Swedberg K., Komajda M., Bohm M., et al. Effects on outcomes of heart rate reduction by ivabradine in patients with congestive heart failure: is there an influence of beta-blocker dose? Findings from the SHIFT (Systolic Heart failure treatment with the I(f ) inhibitor ivabradine Trial) study. J Am Coll Cardiol. 2012;59:1938-45. DOI:10.1016/j.jacc.2012.01.020.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Kannel W.B., Kannel C., Paffenbarger R.S., Cupples L.A. Heart rate and cardiovascular mortality: the Framingham Study. Am Heart J. 1987;113:1489-94. DOI:10.1016/0002-8703(87)90666-1.</mixed-citation><mixed-citation xml:lang="en">Kannel W.B., Kannel C., Paffenbarger R.S., Cupples L.A. Heart rate and cardiovascular mortality: the Framingham Study. Am Heart J. 1987;113:1489-94. DOI:10.1016/0002-8703(87)90666-1.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Fox K.M., Ferrari R. Heart rate: a forgotten link in coronary artery disease? Nat Rev Cardiol. 2011;8:369-79. DOI:10.1038/nrcardio.2011.58.</mixed-citation><mixed-citation xml:lang="en">Fox K.M., Ferrari R. Heart rate: a forgotten link in coronary artery disease? Nat Rev Cardiol. 2011;8:369-79. DOI:10.1038/nrcardio.2011.58.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Комиссаренко И.А., Самсонова Н.Г. Оценка эффективности и переносимости ивабрадина (кораксана) у больных ишемической болезнью сердца с метаболическим синдромом. Эффективная Фармакотерапия. 2013;43:22-7.</mixed-citation><mixed-citation xml:lang="en">Komissarenko I.A., Samsonova N.G. Evaluation of the effectiveness and tolerance of ivabradine (coraxan) in patients with ischemic heart disease with metabolic syndrome. Effektivnaja Farmakoterapija. 2013;43:22-7 (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Fox K., Ford K., Steg P.G., et al. Bradycardia and atrial fibrillation in patients with stable coronary artery disease treated with ivabradine: an analysis from the SIGNIFY study. Eur Heart J. 2015;36(46):3291-6. DOI:10.1093/eurheartj/ehv451.</mixed-citation><mixed-citation xml:lang="en">Fox K., Ford K., Steg P.G., et al. Bradycardia and atrial fibrillation in patients with stable coronary artery disease treated with ivabradine: an analysis from the SIGNIFY study. Eur Heart J. 2015;36(46):3291-6. DOI:10.1093/eurheartj/ehv451.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Васюк Ю.А., Несветов В.В., Школьник Е.Л., и др. Возможности селективного ингибитора ионных f-каналов синусового узла ивабрадина в профилактике антрациклиновой кардиотоксичности у больных раком молочной железы. Рациональная Фармакотерапия в Кардиологии. 2017;13(2):184-90. DOI:10.20996/1819-6446-2017-13-2-184-190.</mixed-citation><mixed-citation xml:lang="en">Vasyuk Y.A., Nesvetov V.V., Shkolnik E.L., et al. Possibilities of Ivabradine, a Selective Inhibitor of IonfChannels of Sinus Node, in Prevention of Anthracycline Cardiotoxicity in Patients with Breast Cancer. Rational Pharmacotherapy in Cardiology. 2017;13(2):184-90 (In Russ.) DOI:10.20996/1819-6446-2017-13-2-184-190.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Martin R.I., Pogoryelova O., Koref M.S., et al. Atrial fibrillation associated with ivabradine treatment: meta-analysis of randomised controlled trials. Heart. 2014;100(19):1506-10. DOI:10.1136/ heartjnl-2014-305482.</mixed-citation><mixed-citation xml:lang="en">Martin R.I., Pogoryelova O., Koref M.S., et al. Atrial fibrillation associated with ivabradine treatment: meta-analysis of randomised controlled trials. Heart. 2014;100(19):1506-10. DOI:10.1136/heartjnl-2014-305482.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Wongcharoen W., Ruttanaphol A., Gunapam S., Phromminitikul A. Ivabradine reduced ventricular rate in patients with non-paroxysmal atrial fibrillation. A Int Cardiol. 2016;224:252-5. DOI:10.1016/j.ijcard.2016.09.044.</mixed-citation><mixed-citation xml:lang="en">Wongcharoen W., Ruttanaphol A., Gunapam S., Phromminitikul A. Ivabradine reduced ventricular rate in patients with non-paroxysmal atrial fibrillation. A Int Cardiol. 2016;224:252-5. DOI:10.1016/j.ijcard.2016.09.044.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Mert K.U., Mert G.O., Morrad B., et al. Effects of ivabradine and beta-blocker therapy on dobutamine-induced ventricular arrhythmias. Kardiol Pol. 2017;75(8):786-93. DOI:10.5603/KP.a2017.0094.</mixed-citation><mixed-citation xml:lang="en">Mert K.U., Mert G.O., Morrad B., et al. Effects of ivabradine and beta-blocker therapy on dobutamine-induced ventricular arrhythmias. Kardiol Pol. 2017;75(8):786-93. DOI:10.5603/KP.a2017.0094.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Werdan K., Ebelt H., Nuding S., et al. Ivabradine in combination with beta-blocker improves symptoms and quality of life in patients with stable angina pectoris: results from the ADDITIONS study. Clin Res Cardiol. 2012;101:365-73. DOI:10.1007/s00392-011-0402-4.</mixed-citation><mixed-citation xml:lang="en">Werdan K., Ebelt H., Nuding S., et al. Ivabradine in combination with beta-blocker improves symptoms and quality of life in patients with stable angina pectoris: results from the ADDITIONS study. Clin Res Cardiol. 2012;101:365-73. DOI:10.1007/s00392-011-0402-4.</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>
