<?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">10.20996/1819-6446-2020-06-10</article-id><article-id custom-type="elpub" pub-id-type="custom">rpcardio-2227</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>CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>АКТУАЛЬНЫЕ  ВОПРОСЫ  КЛИНИЧЕСКОЙ ФАРМАКОЛОГИИ</subject></subj-group></article-categories><title-group><article-title>The Possibilities of Single-Pill Combinations of Antihypertensive Drugs in Cerebroprotection: Focus on the Combination of Amlodipine with Ramipril</article-title><trans-title-group xml:lang="ru"><trans-title>Возможности фиксированных комбинаций антигипертензивных препаратов в церебропротекции: фокус на комбинацию амлодипина и рамиприла</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>Кочетков</surname><given-names>А. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Kochetkov</surname><given-names>A. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кочетков Алексей Иванович - кандидат медицинских наук, доцент, кафедра терапии и полиморбидной патологии, РМАНПО.</p><p>125993, Москва, ул. Баррикадная, 2/1.</p></bio><bio xml:lang="en"><p>Alexey I. Kochetkov - MD, PhD, Associate Professor, Chair of Therapy and Polymorbid Pathology, Russian Medical Academy of Continuous Professional Education.</p><p>Barrikadnaya ul. 2/1, Moscow, 125993.</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>Батюкина</surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Batyukina</surname><given-names>S. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Батюкина Светлана Владимировна - ординатор, кафедра терапии и полиморбидной патологии, РМАНПО.</p><p>125993, Москва, ул. Баррикадная, 2/1.</p></bio><bio xml:lang="en"><p>Svetlana V. Batyukina - Resident, Chair of Therapy and Polymorbid Pathology, Russian Medical Academy of Continuous Professional Education.</p><p>Barrikadnaya ul. 2/1, Moscow, 125993.</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>Остроумова</surname><given-names>О. Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Ostroumova</surname><given-names>O. D.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Остроумова Ольга Дмитриевна - доктор медицинских наук, профессор, заведующая кафедрой терапии и полиморбидной патологии, РМАНПО; профессор, кафедра клинической фармакологии и пропедевтики внутренних болезней, Сеченовский Университет.</p><p>125993, Москва, ул. Баррикадная, 2/1; 119991, Москва, ул. Трубецкая, 8 стр. 2.</p></bio><bio xml:lang="en"><p>Olga D. Ostroumova - MD, PhD, Professor, Head of Chair of Therapy and Polymorbid Pathology, Russian Medical Academy of Continuous Professional Education; Professor, Chair of Clinical Pharmacology and Propaedeutics of Internal Medicine, Sechenov University.</p><p>Barrikadnaya ul. 2/1, Moscow, 125993; Trubetskaya ul. 8-2, Moscow, 119991.</p></bio><email xlink:type="simple">ostroumova.olga@mail.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Назранова</surname><given-names>М. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Nazranova</surname><given-names>M. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Назранова Марианна Юрьевна - студентка, Сеченовский Университет.</p><p>119991, Москва, ул. Трубецкая, 8 стр. 2.</p></bio><bio xml:lang="en"><p>Marianna Yu. Nazranova - Student, Sechenov University.</p><p>Trubetskaya ul. 8-2, Moscow, 119991.</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>Буторов</surname><given-names>В. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Butorov</surname><given-names>V. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Буторов Василий Николаевич - кандидат медицинских наук, доцент, кафедра терапии и полиморбидной патологии, РМАНПО.</p><p>125993, Москва, ул. Баррикадная, 2/1.</p></bio><bio xml:lang="en"><p>Vasilii N. Butorov - MD, PhD, Associate Professor, Chair of Therapy and Polymorbid Pathology, Russian Medical Academy of Continuous Professional Education.</p><p>Barrikadnayaul. 2/1, Moscow, 125993.</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Российская медицинская академия непрерывного профессионального образования</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Russian Medical Academy of Continuous Professional Education</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Российская медицинская академия непрерывного профессионального образования; Первый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский Университет)</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Russian Medical Academy of Continuous Professional Education; I.M. Sechenov First Moscow State Medical University (Sechenov University)</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>Первый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский Университет)</institution><country>Россия</country></aff><aff xml:lang="en"><institution>I.M. Sechenov First Moscow State Medical University (Sechenov University)</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>04</day><month>07</month><year>2020</year></pub-date><volume>16</volume><issue>3</issue><fpage>487</fpage><lpage>497</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Kochetkov A.I., Batyukina S.V., Ostroumova O.D., Nazranova M.Y., Butorov V.N., 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">Кочетков А.И., Батюкина С.В., Остроумова О.Д., Назранова М.Ю., Буторов В.Н.</copyright-holder><copyright-holder xml:lang="en">Kochetkov A.I., Batyukina S.V., Ostroumova O.D., Nazranova M.Y., Butorov V.N.</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/2227">https://www.rpcardio.online/jour/article/view/2227</self-uri><abstract><p>Stroke remains one of the leading causes of death and disability both worldwide and in Russia. Acute cerebrovascular events have many risk factors, among them the most important is arterial hypertension (AH), which predisposes to the stroke development through the direct effect of increased hydrostatic blood pressure on the brain vascular system, followed by arterial remodeling and an increase in their stiffness. In addition, excessive blood pressure variability, activation of the tissue renin-angiotensin-aldosterone system, as well as target-organ damage - primarily the heart in the form of left ventricular hypertrophy, kidneys in the form of microalbuminuria and decrease in glomerular filtration rates. An additional risk factor for stroke is hyperuricemia, which is included in the current European and Russian guidelines for the management of AH as one of the new risk factors in patients with this disease. The state-of-the-art approach to antihypertensive therapy is the using of antihypertensive single-pill combinations, one of the frontline combinations in the absence of special clinical conditions is a combination of an angiotensin converting enzyme inhibitor and a calcium channel blocker. The reference drugs in both classes due to large body of evidence are ramipril and amlodipine, respectively. These drugs provide a high level of brain protection, not only due to the ultra-long and powerful antihypertensive action, but also through a unique potential in target-organ protection via left ventricular hypertrophy regression, antiatherosclerotic effects and improved endothelial function, renal protection, as well as the ability to decrease uric acid in the blood.</p></abstract><trans-abstract xml:lang="ru"><p>Инсульт остается одной из ведущих причин смертности и инвалидизации как во всем мире, так и в Российской федерации. Острое нарушение мозгового кровообращения имеет множество факторов риска своего развития, среди них важнейшим является артериальная гипертония (АГ), которая предрасполагает к возникновению инсульта посредством прямого воздействия повышенного гидростатического давления крови на сосудистую систему центральной нервной системы с последующим ремоделированием мозговых артериол и повышением их ригидности. Помимо этого, в генезе инсульта на фоне АГ существенное значение имеет избыточная вариабельность артериального давления, активация тканевой ренин-ангиотензин-альдостероновой системы, а также поражение органов-мишеней - в первую очередь - сердца в виде гипертрофии миокарда левого желудочка, почек в виде микроальбуминурии и снижения скорости клубочковой фильтрации. Дополнительным фактором риска инсульта служит гиперурикемия, включенная в действующие Европейские и Российские рекомендации по АГ в число новых факторов риска у пациентов с данным заболеванием. Современным принципом антигипертензивной терапии является назначение фиксированных комбинаций антигипертензивных препаратов, одна из комбинаций первой линии в отсутствии особых клинических ситуаций представлена сочетанием ингибитора ангиотензинпревращающего фермента и антагониста кальция. Эталонными представителями обоих классов по праву являются рамиприл и амлодипин. Данные препараты способны обеспечивать высокий уровень церебропротекции не только благодаря сверхдлительному и мощному антигипертензивному эффекту, но и посредством уникального потенциала в органопротекции в виде регресса гипертрофии миокарда левого желудочка, антиатеросклеротических эффектов и улучшения функции эндотелия, нефропротекции, а также способности снижать уровень мочевой кислоты в крови.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>инсульт</kwd><kwd>артериальная гипертония</kwd><kwd>головной мозг</kwd><kwd>поражение органов мишеней</kwd><kwd>антигипертензивная терапия</kwd><kwd>фиксированные комбинации</kwd><kwd>рамиприл</kwd><kwd>амлодипин</kwd></kwd-group><kwd-group xml:lang="en"><kwd>stroke</kwd><kwd>arterial hypertension</kwd><kwd>brain</kwd><kwd>target organ damage</kwd><kwd>antihypertensive therapy</kwd><kwd>single-pill combination</kwd><kwd>ramipril</kwd><kwd>amlodipine</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Публикация статьи поддержана компанией Эгис, что никоим образом не повлияло на собственное мнение авторов.</funding-statement><funding-statement xml:lang="en">The publication of the article is supported by Egis, but it did not affect own opinion of the authors.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Wajngarten M., Silva G.S. Hypertension and Stroke: Update on Treatment. Eur Cardiol. 2019;14(2):111-5. DOI:10.15420/ecr.2019.11.1.</mixed-citation><mixed-citation xml:lang="en">Wajngarten M., Silva G.S. Hypertension and Stroke: Update on Treatment. Eur Cardiol. 2019;14(2):111-5. DOI:10.15420/ecr.2019.11.1.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Donkor E.S. Stroke in the 21st Century: A Snapshot of the Burden, Epidemiology, and Quality of Life. Stroke Res Treat. 2018;2018:3238165. DOI:10.1155/2018/3238165.</mixed-citation><mixed-citation xml:lang="en">Donkor E.S. Stroke in the 21st Century: A Snapshot of the Burden, Epidemiology, and Quality of Life. Stroke Res Treat. 2018;2018:3238165. DOI:10.1155/2018/3238165.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Pistoia F., Sacco S., Degan D., et al. Hypertension and Stroke: Epidemiological Aspects and Clinical Evaluation. High Blood Press Cardiovasc Prev. 2016;23(1):9-18. DOI:10.1007/s40292-015-0115-2.</mixed-citation><mixed-citation xml:lang="en">Pistoia F., Sacco S., Degan D., et al. Hypertension and Stroke: Epidemiological Aspects and Clinical Evaluation. High Blood Press Cardiovasc Prev. 2016;23(1):9-18. DOI:10.1007/s40292-015-0115-2.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Отбить удар: в Минздраве заявили о снижении смертности от инсульта [цитировано 20.01.2020]. Доступно на: https://russian.rt.com/russia/article/442868-rossiya-insult-smertnost-snizhenie.</mixed-citation><mixed-citation xml:lang="en">[cited by Jan 20, 2020]. Available from: https://russian.rt.com/russia/article/442868-rossiya-in-sult-smertnost-snizhenie (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Guzik A., Bushnell C. Stroke Epidemiology and Risk Factor Management. Continuum (Minneap Minn). 2017;23(1, Cerebrovascular Disease):15-39. DOI:10.1212/CON.0000000000000416.</mixed-citation><mixed-citation xml:lang="en">Guzik A., Bushnell C. Stroke Epidemiology and Risk Factor Management. Continuum (Minneap Minn). 2017;23(1, Cerebrovascular Disease):15-39. DOI:10.1212/CON.0000000000000416.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Bejot Y. Targeting blood pressure for stroke prevention: current evidence and unanswered questions. J Neurol. 2019 Jun 26. DOI:10.1007/s00415-019-09443-5.</mixed-citation><mixed-citation xml:lang="en">Bejot Y. Targeting blood pressure for stroke prevention: current evidence and unanswered questions. J Neurol. 2019 Jun 26. DOI:10.1007/s00415-019-09443-5.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Peixoto A.J, White W.B. Circadian blood pressure: clinical implications based on the pathophysiology of its variability. Kidney Int. 2007;71(9):855-60. DOI:10.1038/sj.ki.5002130.</mixed-citation><mixed-citation xml:lang="en">Peixoto A.J, White W.B. Circadian blood pressure: clinical implications based on the pathophysiology of its variability. Kidney Int. 2007;71(9):855-60. DOI:10.1038/sj.ki.5002130.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Elliott WJ. Circadian variation in the timing of stroke onset. А meta-analysis. Stroke. 1998;29:992-6. DOI:10.1161/01.STR.29.5.992.</mixed-citation><mixed-citation xml:lang="en">Elliott WJ. Circadian variation in the timing of stroke onset. А meta-analysis. Stroke. 1998;29:992-6. DOI:10.1161/01.STR.29.5.992.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Kario K. Morning surge in blood pressure and cardiovascular risk: evidence and perspectives. Hypertension. 2010;56(5):765-73. DOI:10.1161/HYPERTENSIONAHA.110.157149.</mixed-citation><mixed-citation xml:lang="en">Kario K. Morning surge in blood pressure and cardiovascular risk: evidence and perspectives. Hypertension. 2010;56(5):765-73. DOI:10.1161/HYPERTENSIONAHA.110.157149.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Dahlof B., Sever P.S., Poulter N.R. et al.; ASCOT Investigators. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-BPLA): a multicentre randomized controlled trial. Lancet. 2005;366:895-906. DOI:10.1016/S0140-6736(05)67185-1.</mixed-citation><mixed-citation xml:lang="en">Dahlof B., Sever P.S., Poulter N.R. et al.; ASCOT Investigators. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-BPLA): a multicentre randomized controlled trial. Lancet. 2005;366:895-906. DOI:10.1016/S0140-6736(05)67185-1.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">O'Leary D.H., Polak J.F., Kronmal R.A., et al. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med. 1999;340(1):14-22. DOI:10.1056/NEJM199901073400103.</mixed-citation><mixed-citation xml:lang="en">O'Leary D.H., Polak J.F., Kronmal R.A., et al. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med. 1999;340(1):14-22. DOI:10.1056/NEJM199901073400103.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Hollander M., Bots M.L., Del Sol A.I., et al. Carotid plaques increase the risk of stroke and subtypes of cerebral infarction in asymptomatic elderly: the Rotterdam study. Circulation. 2002;105(24):2872-7. DOI:10.1161/01.cir.0000018650.58984.75.</mixed-citation><mixed-citation xml:lang="en">Hollander M., Bots M.L., Del Sol A.I., et al. Carotid plaques increase the risk of stroke and subtypes of cerebral infarction in asymptomatic elderly: the Rotterdam study. Circulation. 2002;105(24):2872-7. DOI:10.1161/01.cir.0000018650.58984.75.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">van Sloten T.T., Stehouwer C.D. Carotid Stiffness: A Novel Cerebrovascular Disease Risk Factor. Pulse (Basel). 2016;4(1):24-27. DOI:10.1159/000445354.</mixed-citation><mixed-citation xml:lang="en">van Sloten T.T., Stehouwer C.D. Carotid Stiffness: A Novel Cerebrovascular Disease Risk Factor. Pulse (Basel). 2016;4(1):24-27. DOI:10.1159/000445354.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Mitchell G.F. Effects of central arterial aging on the structure and function of the peripheral vasculature: implications for end-organ damage. J Appl Physiol. 2008;105:1652-60. DOI:10.1152/jap-plphysiol.90549.2008.</mixed-citation><mixed-citation xml:lang="en">Mitchell G.F. Effects of central arterial aging on the structure and function of the peripheral vasculature: implications for end-organ damage. J Appl Physiol. 2008;105:1652-60. DOI:10.1152/jap-plphysiol.90549.2008.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">O'Rourke M.F., Safar M.E. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension. 2005;46:200-4. DOI:10.1161/01.HYP.0000168052.00426.65.</mixed-citation><mixed-citation xml:lang="en">O'Rourke M.F., Safar M.E. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension. 2005;46:200-4. DOI:10.1161/01.HYP.0000168052.00426.65.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Tzourio C., Laurent S., Debette S. Is hypertension associated with an accelerated aging of the brain? Hypertension. 2014;63:894-903. DOI:10.1161/HYPERTENSIONAHA.113.00147.</mixed-citation><mixed-citation xml:lang="en">Tzourio C., Laurent S., Debette S. Is hypertension associated with an accelerated aging of the brain? Hypertension. 2014;63:894-903. DOI:10.1161/HYPERTENSIONAHA.113.00147.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Verdecchia P., Porcellati C., Reboldi G., et al. Left ventricular hypertrophy as an independent predictor of acute cerebrovascular events in essential hypertension. Circulation. 2001;104(17):2039-44. DOI:10.1161/hc4201.097944.</mixed-citation><mixed-citation xml:lang="en">Verdecchia P., Porcellati C., Reboldi G., et al. Left ventricular hypertrophy as an independent predictor of acute cerebrovascular events in essential hypertension. Circulation. 2001;104(17):2039-44. DOI:10.1161/hc4201.097944.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Luft F.C., Agrawal B. Microalbuminuria as a predictive factor for cardiovascular events. J Cardiovasc Pharmacol. 1999;33 Suppl 1:S11-5. DOI:10.1097/00005344-199900001-00003.</mixed-citation><mixed-citation xml:lang="en">Luft F.C., Agrawal B. Microalbuminuria as a predictive factor for cardiovascular events. J Cardiovasc Pharmacol. 1999;33 Suppl 1:S11-5. DOI:10.1097/00005344-199900001-00003.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Ettehad D., Emdin C.A., Kiran A., et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016;387(10022):957-67. DOI:10.1016/S0140-6736(15)01225-8.</mixed-citation><mixed-citation xml:lang="en">Ettehad D., Emdin C.A., Kiran A., et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016;387(10022):957-67. DOI:10.1016/S0140-6736(15)01225-8.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Rutan G.H., Kuller L.H., Neaton J.D., et al. Mortality associated with diastolic hypertension and isolated systolic hypertension among men screened for the Multiple Risk Factor Intervention Trial. Circulation. 1988;77(3):504-14. DOI:10.1161/01.cir.77.3.504.</mixed-citation><mixed-citation xml:lang="en">Rutan G.H., Kuller L.H., Neaton J.D., et al. Mortality associated with diastolic hypertension and isolated systolic hypertension among men screened for the Multiple Risk Factor Intervention Trial. Circulation. 1988;77(3):504-14. DOI:10.1161/01.cir.77.3.504.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Williams B., Mancia G., Spiering W., et al.; ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension. The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur Heart J. 2018;39(33):3021-104. DOI:10.1093/eurheartj/ehy339.</mixed-citation><mixed-citation xml:lang="en">Williams B., Mancia G., Spiering W., et al.; ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension. The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur Heart J. 2018;39(33):3021-104. DOI:10.1093/eurheartj/ehy339.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Рубрикатор клинических рекомендаций Минздрава Российской федерации: клинические рекомендации «Артериальная гипертензия у взрослых» [цитировано 20.01.2020]. Доступно на: http://cr.rosminzdrav.ru/#!/recomend/687.</mixed-citation><mixed-citation xml:lang="en">Categories of clinical guidelines of Ministry of Health of the Russian Federation: clinical guidelines “Arterial hypertension in adults” [cited by Jan 20, 2020]. Available from: http://cr.rosminzdrav.ru/ #!/recomend/687 (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Vasudeva K., Balyan R., Munshi A. ACE-Triggered Hypertension Incites Stroke: Genetic, Molecular, and Therapeutic Aspects. Neuromolecular Med. 2020;22(2):194-209. DOI:10.1007/s12017-019-08583-1.</mixed-citation><mixed-citation xml:lang="en">Vasudeva K., Balyan R., Munshi A. ACE-Triggered Hypertension Incites Stroke: Genetic, Molecular, and Therapeutic Aspects. Neuromolecular Med. 2020;22(2):194-209. DOI:10.1007/s12017-019-08583-1.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Weir M.R. Targeting mechanisms of hypertensive vascular disease with dual calcium channel and renin-angiotensin system blockade. J Hum Hypertens. 2007;21(10):770-9. DOI:10.1038/sj.jhh.1002254.</mixed-citation><mixed-citation xml:lang="en">Weir M.R. Targeting mechanisms of hypertensive vascular disease with dual calcium channel and renin-angiotensin system blockade. J Hum Hypertens. 2007;21(10):770-9. DOI:10.1038/sj.jhh.1002254.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Neaton J.D., Grimm R.H.Jr, Prineas R.J., et al. Treatment of Mild Hypertension Study. Final results. Treatment of Mild Hypertension Study Research Group. JAMA. 1993;270(6):713-24. DOI:10.1001/jama.1993.03510060059034.</mixed-citation><mixed-citation xml:lang="en">Neaton J.D., Grimm R.H.Jr, Prineas R.J., et al. Treatment of Mild Hypertension Study. Final results. Treatment of Mild Hypertension Study Research Group. JAMA. 1993;270(6):713-24. DOI:10.1001/jama.1993.03510060059034.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Julius S., Kjeldsen S.E., Weber M., et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004;363(9426):2022-31. DOI:10.1016/S0140-6736(04)16451-9.</mixed-citation><mixed-citation xml:lang="en">Julius S., Kjeldsen S.E., Weber M., et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004;363(9426):2022-31. DOI:10.1016/S0140-6736(04)16451-9.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Iadecola C., Gorelick P.B. Hypertension, angiotensin, and stroke: beyond blood pressure. Stroke. 2004;35(2):348-50. DOI:10.1161/01.STR.0000115162.16321.AA.</mixed-citation><mixed-citation xml:lang="en">Iadecola C., Gorelick P.B. Hypertension, angiotensin, and stroke: beyond blood pressure. Stroke. 2004;35(2):348-50. DOI:10.1161/01.STR.0000115162.16321.AA.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Heart Outcomes Prevention Evaluation Study Investigators, Yusuf S, Sleight P, Pogue J et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342(3):145-53. DOI:10.1056/NEJM200001203420301.</mixed-citation><mixed-citation xml:lang="en">Heart Outcomes Prevention Evaluation Study Investigators, Yusuf S, Sleight P, Pogue J et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342(3):145-53. DOI:10.1056/NEJM200001203420301.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Bosch J., Yusuf S., Pogue J., et al. Use of ramipril in preventing stroke: double blind randomised trial. BMJ. 2002;324(7339):699-702. DOI:10.1136/bmj.324.7339.699.</mixed-citation><mixed-citation xml:lang="en">Bosch J., Yusuf S., Pogue J., et al. Use of ramipril in preventing stroke: double blind randomised trial. BMJ. 2002;324(7339):699-702. DOI:10.1136/bmj.324.7339.699.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Rothwell P.M., Howard S.C., Dolan E., et al.; ASCOT-BPLA and MRC Trial Investigators. Effects of beta blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke. Lancet Neurol. 2010;9(5):469-80. DOI:10.1016/S1474-4422(10)70066-1.</mixed-citation><mixed-citation xml:lang="en">Rothwell P.M., Howard S.C., Dolan E., et al.; ASCOT-BPLA and MRC Trial Investigators. Effects of beta blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke. Lancet Neurol. 2010;9(5):469-80. DOI:10.1016/S1474-4422(10)70066-1.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Rothwell P.M., Howard S.C., Dolan E., et al. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure and episodic hypertension. Lancet. 2010;375:895-905. DOI:10.1016/S0140-6736(10)60308-X.</mixed-citation><mixed-citation xml:lang="en">Rothwell P.M., Howard S.C., Dolan E., et al. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure and episodic hypertension. Lancet. 2010;375:895-905. DOI:10.1016/S0140-6736(10)60308-X.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Pitt B., Byington R.P., Furberg C.D., et al. Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. PREVENT Investigators. Circulation. 2000;102(13):1503-1510. DOI:10.1161/01.cir.102.13.1503.</mixed-citation><mixed-citation xml:lang="en">Pitt B., Byington R.P., Furberg C.D., et al. Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. PREVENT Investigators. Circulation. 2000;102(13):1503-1510. DOI:10.1161/01.cir.102.13.1503.</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Nissen S.E., Tuzcu E. M., Libby P., et al. for the CAMELOT Investigators. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure. The CAMELOT study: a randomized controlled trial. JAMA. 2004;292:2217-25. DOI:10.1001/jama.292.18.2217.</mixed-citation><mixed-citation xml:lang="en">Nissen S.E., Tuzcu E. M., Libby P., et al. for the CAMELOT Investigators. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure. The CAMELOT study: a randomized controlled trial. JAMA. 2004;292:2217-25. DOI:10.1001/jama.292.18.2217.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Lonn E., Yusuf S., Dzavik V., et al. Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE). Circulation. 2001;103(7):919-25. DOI:10.1161/01.cir.103.7.919.</mixed-citation><mixed-citation xml:lang="en">Lonn E., Yusuf S., Dzavik V., et al. Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE). Circulation. 2001;103(7):919-25. DOI:10.1161/01.cir.103.7.919.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Подзолков В.И., Тарзиманова А.И. Новая фиксированная комбинация рамиприла и амлодипина в лечении артериальной гипертензии. Рациональная Фармакотерапия в Кардиологии. 2015;11(3):327-32. DOI:10.20996/1819-6446-2015-11-3-327-332.</mixed-citation><mixed-citation xml:lang="en">Podzolkov V.I., Tarzimanova A.I. The new fixed combination of amlodipine and ramipril in the treatment of hypertension. Rational Pharmacotherapy in Cardiology. 2015;11(3):327-32 (In Russ.) DOI:10.20996/1819-6446-2015-11-3-327-332.</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Verdecchia P., Schillaci G., Borgioni C., et al. Prognostic value of a new electrocardiographic method for diagnosis of left ventricular hypertrophy in essential hypertension. J Am Coll Cardiol. 1998;31(2):383-90. DOI:10.1016/s0735-1097(97)00493-2.</mixed-citation><mixed-citation xml:lang="en">Verdecchia P., Schillaci G., Borgioni C., et al. Prognostic value of a new electrocardiographic method for diagnosis of left ventricular hypertrophy in essential hypertension. J Am Coll Cardiol. 1998;31(2):383-90. DOI:10.1016/s0735-1097(97)00493-2.</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Okin P.M., Devereux R.B., Jern S., et al. Regression of electrocardiographic left ventricular hypertrophy by losartan versus atenolol: The Losartan Intervention for Endpoint reduction in Hypertension (LIFE) Study. Circulation. 2003;108(6):684-90. DOI:10.1161/01.CIR.0000083724.28630.C3.</mixed-citation><mixed-citation xml:lang="en">Okin P.M., Devereux R.B., Jern S., et al. Regression of electrocardiographic left ventricular hypertrophy by losartan versus atenolol: The Losartan Intervention for Endpoint reduction in Hypertension (LIFE) Study. Circulation. 2003;108(6):684-90. DOI:10.1161/01.CIR.0000083724.28630.C3.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Wachtell K., Okin P.M., Olsen M.H., et al. Regression of electrocardiographic left ventricular hypertrophy during antihypertensive therapy and reduction in sudden cardiac death: the LIFE Study. Circulation. 2007;116(7):700-5. DOI:10.1161/CIRCULATIONAHA.106.666594.</mixed-citation><mixed-citation xml:lang="en">Wachtell K., Okin P.M., Olsen M.H., et al. Regression of electrocardiographic left ventricular hypertrophy during antihypertensive therapy and reduction in sudden cardiac death: the LIFE Study. Circulation. 2007;116(7):700-5. DOI:10.1161/CIRCULATIONAHA.106.666594.</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Agabiti-Rosei E., Ambrosioni E., Dal Palu C., et al. ACE inhibitor ramipril is more effective than the beta-blocker atenolol in reducing left ventricular mass in hypertension. Results of the RACE (ramipril cardioprotective evaluation) study on behalf of the RACE study group. J Hypertens. 1995;13(11):1325-34. DOI:10.1097/00004872-199511000-00015.</mixed-citation><mixed-citation xml:lang="en">Agabiti-Rosei E., Ambrosioni E., Dal Palu C., et al. ACE inhibitor ramipril is more effective than the beta-blocker atenolol in reducing left ventricular mass in hypertension. Results of the RACE (ramipril cardioprotective evaluation) study on behalf of the RACE study group. J Hypertens. 1995;13(11):1325-34. DOI:10.1097/00004872-199511000-00015.</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Lancet. 1997;349(9069):1857-63. DOI:10.1016/S0140-6736(96)11445-8</mixed-citation><mixed-citation xml:lang="en">The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Lancet. 1997;349(9069):1857-63. DOI:10.1016/S0140-6736(96)11445-8</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Dzau V.J., Bernstein K., Celermajer D., et al. The relevance of tissue angiotensin-converting enzyme: manifestations in mechanistic and endpoint data. Am J Cardiol. 2001;88(9A):1L-20L. DOI:10.1016/s0002-9149(01)01878-1.</mixed-citation><mixed-citation xml:lang="en">Dzau V.J., Bernstein K., Celermajer D., et al. The relevance of tissue angiotensin-converting enzyme: manifestations in mechanistic and endpoint data. Am J Cardiol. 2001;88(9A):1L-20L. DOI:10.1016/s0002-9149(01)01878-1.</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Meisel S, Shamiss A, Rosenthal T. Clinical pharmacokinetics of ramipril. Clin Pharmacokinet. 1994;26(1):7-15. DOI:10.2165/00003088-199426010-00002.</mixed-citation><mixed-citation xml:lang="en">Meisel S, Shamiss A, Rosenthal T. Clinical pharmacokinetics of ramipril. Clin Pharmacokinet. 1994;26(1):7-15. DOI:10.2165/00003088-199426010-00002.</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Остроумова О.Д., Максимов М.Л., Бондарец О.В. Ингибиторы ангиотензинпревращающего фермента в практике врача: сходства и различия. Медицинский Совет. 2011;5-6:50-7.</mixed-citation><mixed-citation xml:lang="en">Ostroumova O.D., Maksimov M.L., Bondarets O.V. Angiotensin-converting enzyme inhibitors in the physician's practice: similarities and differences. Meditsinskiy Sovet. 2011;5-6:50-7 (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Jamerson K., Weber M.A., Bakris G.L., et al. for the Accomplish trial investigators. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008;359:2417-2428. DOI:10.1056/NEJMoa0806182.</mixed-citation><mixed-citation xml:lang="en">Jamerson K., Weber M.A., Bakris G.L., et al. for the Accomplish trial investigators. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008;359:2417-2428. DOI:10.1056/NEJMoa0806182.</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Bakris G.L., Sarafidis P.A., Weir M.R., et al. Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial. Lancet. 2010;375(9721):1173-81. DOI:10.1016/S0140-6736(09)62100-0.</mixed-citation><mixed-citation xml:lang="en">Bakris G.L., Sarafidis P.A., Weir M.R., et al. Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial. Lancet. 2010;375(9721):1173-81. DOI:10.1016/S0140-6736(09)62100-0.</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Lehto S., Niskanen L., Ronnemaa T., Laakso M. Serum uric acid is a strong predictor of stroke in patients with non-insulin-dependent diabetes mellitus. Stroke. 1998;29(3):635-9. DOI:10.1161/01.str.29.3.635.</mixed-citation><mixed-citation xml:lang="en">Lehto S., Niskanen L., Ronnemaa T., Laakso M. Serum uric acid is a strong predictor of stroke in patients with non-insulin-dependent diabetes mellitus. Stroke. 1998;29(3):635-9. DOI:10.1161/01.str.29.3.635.</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Storhaug H.M., Norvik J.V.., Toft I., et al. Uric acid is a risk factor for ischemic stroke and all-cause mortality in the general population: a gender specific analysis from The Troms0 Study. BMC Cardiovasc Disord. 2013;13:115. DOI:10.1186/1471-2261-13-115.</mixed-citation><mixed-citation xml:lang="en">Storhaug H.M., Norvik J.V.., Toft I., et al. Uric acid is a risk factor for ischemic stroke and all-cause mortality in the general population: a gender specific analysis from The Troms0 Study. BMC Cardiovasc Disord. 2013;13:115. DOI:10.1186/1471-2261-13-115.</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Jacobsen B.K., Eggen A.E., Mathiesen E.B., et al. Cohort profile: the Tromso Study. Int J Epidemiol. 2012;41(4):961-7. DOI:10.1093/ije/dyr049.</mixed-citation><mixed-citation xml:lang="en">Jacobsen B.K., Eggen A.E., Mathiesen E.B., et al. Cohort profile: the Tromso Study. Int J Epidemiol. 2012;41(4):961-7. DOI:10.1093/ije/dyr049.</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Tomcsany J.A. Ramipriles Amlodipin kombinacio vernyomascsokkento hatekonysaganak MOni-torozasa es beavatkozassal Nem jaro Adatgyujtese (RAMONA tanulmany). Hypertonia es Nephrologia, 2013;17:49-96.</mixed-citation><mixed-citation xml:lang="en">Tomcsany J.A. Ramipriles Amlodipin kombinacio vernyomascsokkento hatekonysaganak MOni-torozasa es beavatkozassal Nem jaro Adatgyujtese (RAMONA tanulmany). Hypertonia es Nephrologia, 2013;17:49-96.</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Остроумова О.Д., Зыкова А.А. Эффективность фиксированной комбинации рамиприл/амлодипин в лечении артериальной гипертонии, хронической болезни почек и сахарного диабета. Медицинский Совет. 2016;13:16-23. DOI:10.21518/2079-701X-2016-13-16-23.</mixed-citation><mixed-citation xml:lang="en">Ostroumova O.D., Zykov A.A. Effectiveness of fixed combination of ramipil/amlodipine in therapy of arterial hypertension, chronic kidney disease and diabetes mellitus. Meditsinskiy Sovet. 2016;13:16-23 (In Russ.) DOI:10.21518/2079-701X-2016-13-16-23.</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>
