<?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="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">fcmedicine</journal-id><journal-title-group><journal-title xml:lang="ru">Фундаментальная и клиническая медицина</journal-title><trans-title-group xml:lang="en"><trans-title>Fundamental and Clinical Medicine</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2500-0764</issn><issn pub-type="epub">2542-0941</issn><publisher><publisher-name>КемГМУ</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.23946/2500-0764-2021-6-1-60-68</article-id><article-id custom-type="elpub" pub-id-type="custom">fcmedicine-374</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОБЗОРНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEW ARTICLES</subject></subj-group></article-categories><title-group><article-title>Метаболическая терапия в кардиологии с позиции доказательной медицины</article-title><trans-title-group xml:lang="en"><trans-title>Metabolic therapy in cardiology from the perspective of evidence-based medicine</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0655-1407</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Костин</surname><given-names>И. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kostin</surname><given-names>V. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Костин Владимир Иванович, доктор медицинских наук, профессор кафедры госпитальной терапии и клинической фармакологии</p><p>650056, г. Кемерово, ул. Ворошилова, д. 22а</p></bio><bio xml:lang="en"><p>Vladimir I. Kostin, Prof., MD, DSc, Professor, Department of Clinical Therapy and Clinical Pharmacology</p><p>22a, Voroshilova Street, Kemerovo, 650056</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1686-1254</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шангина</surname><given-names>О. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Shangina</surname><given-names>O. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Шангина Ольга Анатольевна, кандидат медицинских наук, доцент кафедры госпитальной терапии и клинической фармакологии</p><p>650056, г. Кемерово, ул. Ворошилова, д. 22а</p></bio><bio xml:lang="en"><p>Olga A. Shangina, Dr., MD, PhD, Associate Professor, Department of Clinical Therapy and Clinical Pharmacology</p><p>22a, Voroshilova Street, Kemerovo, 650056</p></bio><email xlink:type="simple">shangina@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9568-8818</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шелихов</surname><given-names>В. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Shelikhov</surname><given-names>V. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Шелихов Валентин Григорьевич, кандидат медицинских наук, доцент кафедры госпитальной терапии и клинической фармакологии</p><p>650056, г. Кемерово, ул. Ворошилова, д. 22а</p></bio><bio xml:lang="en"><p>Valentin G. Shelikhov, Dr., MD, PhD, Associate Professor, Department of Clinical Therapy and Clinical Pharmacology</p><p>22a, Voroshilova Street, Kemerovo, 650056</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБОУ ВО «Кемеровский государственный медицинский университет» Министерства здравоохранения Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Kemerovo State Medical University, Kemerovo, Russian Federation</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2021</year></pub-date><pub-date pub-type="epub"><day>28</day><month>03</month><year>2021</year></pub-date><volume>6</volume><issue>1</issue><fpage>60</fpage><lpage>68</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Костин И.В., Шангина О.А., Шелихов В.Г., 2021</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="ru">Костин И.В., Шангина О.А., Шелихов В.Г.</copyright-holder><copyright-holder xml:lang="en">Kostin V.I., Shangina O.A., Shelikhov V.G.</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://fcm.kemsmu.ru/jour/article/view/374">https://fcm.kemsmu.ru/jour/article/view/374</self-uri><abstract><p>В течение нескольких последних десятилетий в медицине интенсивно развивается так называемое «метаболическое» направление. Чаще всего под препаратами «метаболического действия» подразумевают средства, влияющие на кислородозависимые процессы, улучшающие энергетический метаболизм клетки, т.е. повышающие устойчивость тканей к гипоксии и ишемии. Особенно широко подобные препараты пытаются использовать в кардиологии. Вопрос о целесообразности и эффективности применения средств метаболической терапии в настоящее время является одним из наиболее обсуждаемых. Наибольший интерес вызывает использование компонентов дыхательной цепи, пуриновых нуклеозидов, креатинфосфата, препаратов, влияющих на окисление глюкозы и свободных жирных кислот в цикле Кребса. В данном обзоре была предпринята попытка оценить наиболее популярные препараты этой группы (аденозинтрифосфат (АТФ), аденозин-5-монофосфат, креатинфосфат, коэнзим Q10, цитохром С, аденозин, глюкозо-инсулино-калиевая смесь, L-карнитин, милдронат, триметазидин), широко представленные на фармацевтическом рынке, с позиций теоретической обоснованности их применения и клинической эффективности. Несмотря на большое количество доклинических и клинических исследований, вопрос о целесообразности их использования остается нерешенным. С одной стороны, имеется много неясностей в вопросах теоретического обоснования механизма их терапевтического действия, а с другой – целый ряд лекарственных средств, отнесенных к этой группе, не продемонстрировал ожидаемых результатов в клинических условиях. Из всех препаратов подобного типа только триметазидин был включен в европейские и российские рекомендации по лечению стабильной стенокардии как препарат второй линии. Проблема заключается в том, что в большинстве клинических исследований оценка терапевтической эффективности этих препаратов проводилась только по так называемым суррогатным конечным точкам. Тем не менее препараты этой группы активно рекламируются и достаточно широко применяются в практической деятельности. Однако до сих пор ни один препарат из этой группы не имеет убедительной доказательной базы характера его влияния на прогноз пациентов (смертность и/или основные неблагоприятные сердечно-сосудистые события). Для получения этих доказательств необходимо дальнейшее их изучение в рамках крупномасштабных рандомизированных исследований.</p></abstract><trans-abstract xml:lang="en"><p>Over the past few decades, various applications of the metabolic drugs have been extensively tested. Most of them affect oxygen-dependent processes, improving cellular metabolism and increasing tissue resistance to hypoxia and ischemia. The most promising candidates include components of the respiratory chain, purine nucleosides, and creatine phosphate which affect glucose oxidation and fatty acid metabolism in the Krebs cycle. This review critically evaluates the most popular drugs of this group (adenosine triphosphate, adenosine-5-monophosphate, creatine phosphate, coenzyme Q10, cytochrome C, adenosine, glucose-insulin-potassium solution, L-carnitine, mildronate, and trimetazidine), which are widely represented on the pharmaceutical market. Of all metabolic drugs, only trimetazidine was included in the European and Russian recommendations for the second-line treatment of stable angina. In most clinical studies, the therapeutic efficacy of metabolic drugs has been evaluated using the surrogate endpoints. Despite being actively advertised and widely used in the clinical practice, metabolic drugs currently do not have a convincing evidence base for affecting prognosis (mortality and/or major adverse cardiovascular events). Further studies in large-scale randomised trials are needed to confirm the beneficial effects of the metabolic drugs in cardiovascular medicine.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>метаболическая терапия</kwd><kwd>кардиология</kwd><kwd>стенокардия</kwd><kwd>клинические исследования</kwd><kwd>эффективность</kwd></kwd-group><kwd-group xml:lang="en"><kwd>Metabolic therapy</kwd><kwd>cardiology</kwd><kwd>angina</kwd><kwd>clinical studies</kwd><kwd>efficacy</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">Grivennikova VG, Vinogradov AD. Mitochondrial production of reactive oxygen species. Biochemistry (Mosc). 2013;78(13):1490- 511. https://dx.doi.org/10.1134/S0006297913130087</mixed-citation><mixed-citation xml:lang="en">Grivennikova VG, Vinogradov AD. Mitochondrial production of reactive oxygen species. Biochemistry (Mosc). 2013;78(13):1490- 511. https://dx.doi.org/10.1134/S0006297913130087</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Neubauer S. The failing heart--an engine out of fuel. N Engl J Med. 2007;356(11):1140-1151. https://dx.doi.org/10.1056/NEJMra063052</mixed-citation><mixed-citation xml:lang="en">Neubauer S. The failing heart--an engine out of fuel. N Engl J Med. 2007;356(11):1140-1151. https://dx.doi.org/10.1056/NEJMra063052</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Gatsura VV. Pharmacological correction of the energy metabolism of the ischemic myocardium. Pharmacol Ther. 1985;27(3):297- 332. https://dx.doi.org/10.1016/0163-7258(85)90073-7</mixed-citation><mixed-citation xml:lang="en">Gatsura VV. Pharmacological correction of the energy metabolism of the ischemic myocardium. Pharmacol Ther. 1985;27(3):297- 332. https://dx.doi.org/10.1016/0163-7258(85)90073-7</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Borea PA, Gessi S, Merighi S, Vincenzi F, Varani K. Pharmacology of Adenosine Receptors: The State of the Art. Physiol Rev. 2018;98(3):1591-1625. https://dx.doi.org/10.1152/physrev.00049.2017</mixed-citation><mixed-citation xml:lang="en">Borea PA, Gessi S, Merighi S, Vincenzi F, Varani K. Pharmacology of Adenosine Receptors: The State of the Art. Physiol Rev. 2018;98(3):1591-1625. https://dx.doi.org/10.1152/physrev.00049.2017</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Wallimann T, Tokarska-Schlattner M, Schlattner U. The creatine kinase system and pleiotropic effects of creatine. Amino Acids. 2011;40(5):1271-1296. https://dx.doi.org/10.1007/s00726-011-0877-3</mixed-citation><mixed-citation xml:lang="en">Wallimann T, Tokarska-Schlattner M, Schlattner U. The creatine kinase system and pleiotropic effects of creatine. Amino Acids. 2011;40(5):1271-1296. https://dx.doi.org/10.1007/s00726-011-0877-3</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Ke-Wu D, Xu-Bo S, Ying-Xin Z, Shi-Wei Y, Yu-Jie Z, DongMei S, Yu-Yang L, De-An J, Zhe F, Zhi-Ming Z, Hai-Long G, Zhen-Xian Y, Chang-Sheng M. The effect of exogenous creatine phosphate on myocardial injury after percutaneous coronary intervention. Angiology. 2015;66(2):163-8. https://dx.doi.org/10.1177/0003319713515996</mixed-citation><mixed-citation xml:lang="en">Ke-Wu D, Xu-Bo S, Ying-Xin Z, Shi-Wei Y, Yu-Jie Z, DongMei S, Yu-Yang L, De-An J, Zhe F, Zhi-Ming Z, Hai-Long G, Zhen-Xian Y, Chang-Sheng M. The effect of exogenous creatine phosphate on myocardial injury after percutaneous coronary intervention. Angiology. 2015;66(2):163-8. https://dx.doi.org/10.1177/0003319713515996</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Landoni G, Zangrillo A, Lomivorotov VV, Likhvantsev V, Ma J, De Simone F, Fominskiy E. Cardiac protection with phosphocreatine: a meta-analysis. Interact Cardiovasc Thorac Surg. 2016;23(4):637-646. https://dx.doi.org/10.1093/icvts/ivw171</mixed-citation><mixed-citation xml:lang="en">Landoni G, Zangrillo A, Lomivorotov VV, Likhvantsev V, Ma J, De Simone F, Fominskiy E. Cardiac protection with phosphocreatine: a meta-analysis. Interact Cardiovasc Thorac Surg. 2016;23(4):637-646. https://dx.doi.org/10.1093/icvts/ivw171</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Akbari A, Mobini GR, Agah S, Morvaridzadeh M, Omidi A, Potter E, Fazelian S, Ardehali SH, Daneshzad E, Dehghani S. Coenzyme Q10 supplementation and oxidative stress parameters: a systematic review and meta-analysis of clinical trials. Eur J Clin Pharmacol. 2020;76(11):1483-1499. https://dx.doi.org/10.1007/s00228-020-02919-8</mixed-citation><mixed-citation xml:lang="en">Akbari A, Mobini GR, Agah S, Morvaridzadeh M, Omidi A, Potter E, Fazelian S, Ardehali SH, Daneshzad E, Dehghani S. Coenzyme Q10 supplementation and oxidative stress parameters: a systematic review and meta-analysis of clinical trials. Eur J Clin Pharmacol. 2020;76(11):1483-1499. https://dx.doi.org/10.1007/s00228-020-02919-8</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Zozina VI, Covantev S, Goroshko OA, Krasnykh LM, Kukes VG. Coenzyme Q10 in Cardiovascular and Metabolic Diseases: Current State of the Problem. Curr Cardiol Rev. 2018;14(3):164-174. https://dx.doi.org/10.2174/1573403X14666180416115428</mixed-citation><mixed-citation xml:lang="en">Zozina VI, Covantev S, Goroshko OA, Krasnykh LM, Kukes VG. Coenzyme Q10 in Cardiovascular and Metabolic Diseases: Current State of the Problem. Curr Cardiol Rev. 2018;14(3):164-174. https://dx.doi.org/10.2174/1573403X14666180416115428</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Di Lorenzo A, Iannuzzo G, Parlato A, Cuomo G, Testa C, Coppola M, D'Ambrosio G, Oliviero DA, Sarullo S, Vitale G, Nugara C, Sarullo FM, Giallauria F. Clinical Evidence for Q10 Coenzyme Supplementation in Heart Failure: From Energetics to Functional Improvement. J Clin Med. 2020;9(5):1266. https://dx.doi.org/10.3390/jcm9051266</mixed-citation><mixed-citation xml:lang="en">Di Lorenzo A, Iannuzzo G, Parlato A, Cuomo G, Testa C, Coppola M, D'Ambrosio G, Oliviero DA, Sarullo S, Vitale G, Nugara C, Sarullo FM, Giallauria F. Clinical Evidence for Q10 Coenzyme Supplementation in Heart Failure: From Energetics to Functional Improvement. J Clin Med. 2020;9(5):1266. https://dx.doi.org/10.3390/jcm9051266</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Morisco C, Trimarco B, Condorelli M. Effect of coenzyme Q10 therapy in patients with congestive heart failure: a long-term multicenter randomized study. Clin Investig. 1993;71(8 Suppl):S134-136. https://dx.doi.org/10.1007/BF00226854</mixed-citation><mixed-citation xml:lang="en">Morisco C, Trimarco B, Condorelli M. Effect of coenzyme Q10 therapy in patients with congestive heart failure: a long-term multicenter randomized study. Clin Investig. 1993;71(8 Suppl):S134-136. https://dx.doi.org/10.1007/BF00226854</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Sharma A, Fonarow GC, Butler J, Ezekowitz JA, Felker GM. Coenzyme Q10 and Heart Failure: A State-of-the-Art Review. Circ Heart Fail. 2016;9(4):e002639. https://dx.doi.org/10.1161/CIRCHEARTFAILURE.115.002639</mixed-citation><mixed-citation xml:lang="en">Sharma A, Fonarow GC, Butler J, Ezekowitz JA, Felker GM. Coenzyme Q10 and Heart Failure: A State-of-the-Art Review. Circ Heart Fail. 2016;9(4):e002639. https://dx.doi.org/10.1161/CIRCHEARTFAILURE.115.002639</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Mortensen SA, Rosenfeldt F, Kumar A, Dolliner P, Filipiak KJ, Pella D, Alehagen U, Steurer G, Littarru GP; Q-SYMBIO Study Investigators. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial. JACC Heart Fail. 2014;2(6):641-649. https://dx.doi.org/10.1016/j.jchf.2014.06.008</mixed-citation><mixed-citation xml:lang="en">Mortensen SA, Rosenfeldt F, Kumar A, Dolliner P, Filipiak KJ, Pella D, Alehagen U, Steurer G, Littarru GP; Q-SYMBIO Study Investigators. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial. JACC Heart Fail. 2014;2(6):641-649. https://dx.doi.org/10.1016/j.jchf.2014.06.008</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Mortensen AL, Rosenfeldt F, Filipiak KJ. Effect of coenzyme Q10 in Europeans with chronic heart failure: A sub-group analysis of the Q-SYMBIO randomized double-blind trial. Cardiol J. 2019;26(2):147-156. https://dx.doi.org/10.5603/CJ.a2019.0022</mixed-citation><mixed-citation xml:lang="en">Mortensen AL, Rosenfeldt F, Filipiak KJ. Effect of coenzyme Q10 in Europeans with chronic heart failure: A sub-group analysis of the Q-SYMBIO randomized double-blind trial. Cardiol J. 2019;26(2):147-156. https://dx.doi.org/10.5603/CJ.a2019.0022</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Madmani ME, Yusuf Solaiman A, Tamr Agha K, Madmani Y, Shahrour Y, Essali A, Kadro W. Coenzyme Q10 for heart failure. Cochrane Database Syst Rev. 2014;(6):CD008684. https://dx.doi.org/10.1002/14651858.CD008684.pub2</mixed-citation><mixed-citation xml:lang="en">Madmani ME, Yusuf Solaiman A, Tamr Agha K, Madmani Y, Shahrour Y, Essali A, Kadro W. Coenzyme Q10 for heart failure. Cochrane Database Syst Rev. 2014;(6):CD008684. https://dx.doi.org/10.1002/14651858.CD008684.pub2</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Lei L, Liu Y. Effcacy of coenzyme Q10 in patients with cardiac failure: a meta-analysis of clinical trials. BMC Cardiovasc Disord. 2017;17(1):196. https://dx.doi.org/10.1186/s12872-017-0628-9</mixed-citation><mixed-citation xml:lang="en">Lei L, Liu Y. Effcacy of coenzyme Q10 in patients with cardiac failure: a meta-analysis of clinical trials. BMC Cardiovasc Disord. 2017;17(1):196. https://dx.doi.org/10.1186/s12872-017-0628-9</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Trongtorsak A, Kongnatthasate K, Susantitaphong P, Kittipibul V, Ariyachaipanich A. Effect of Coenzyme Q10 on left ventricular remodeling and mortality in patients with heart failure: A meta-analysis. J Am Coll Cardiol. 2017;69(11):707. https://doi.org/10.1016/S0735-1097(17)34096-2</mixed-citation><mixed-citation xml:lang="en">Trongtorsak A, Kongnatthasate K, Susantitaphong P, Kittipibul V, Ariyachaipanich A. Effect of Coenzyme Q10 on left ventricular remodeling and mortality in patients with heart failure: A meta-analysis. J Am Coll Cardiol. 2017;69(11):707. https://doi.org/10.1016/S0735-1097(17)34096-2</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Alehagen U, Aaseth J, Alexander J, Johansson P. Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly. PLoS One. 2018;13(4):e0193120. https://doi.org/10.1371/journal.pone.0193120</mixed-citation><mixed-citation xml:lang="en">Alehagen U, Aaseth J, Alexander J, Johansson P. Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly. PLoS One. 2018;13(4):e0193120. https://doi.org/10.1371/journal.pone.0193120</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Flowers N, Hartley L, Todkill D, Stranges S, Rees K. Co-enzyme Q10 supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2014;(12):CD010405. https://doi.org/10.1002/14651858.CD010405.pub2</mixed-citation><mixed-citation xml:lang="en">Flowers N, Hartley L, Todkill D, Stranges S, Rees K. Co-enzyme Q10 supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2014;(12):CD010405. https://doi.org/10.1002/14651858.CD010405.pub2</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Santucci R, Sinibaldi F, Cozza P, Polticelli F, Fiorucci L. Cytochrome c: An extreme multifunctional protein with a key role in cell fate. Int J Biol Macromol. 2019;136:1237-1246. https://doi.org/10.1016/j.ijbiomac.2019.06.180</mixed-citation><mixed-citation xml:lang="en">Santucci R, Sinibaldi F, Cozza P, Polticelli F, Fiorucci L. Cytochrome c: An extreme multifunctional protein with a key role in cell fate. Int J Biol Macromol. 2019;136:1237-1246. https://doi.org/10.1016/j.ijbiomac.2019.06.180</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Ивкин Д.Ю., Оковитый С.В. Патогенетическая терапия состояний гипоксии органов и тканей на клеточном уровне. Лечащий врач. 2017;7:11 https://www.lvrach.ru/2017/07/15436757</mixed-citation><mixed-citation xml:lang="en">Ivkin DJu, Okovityj SV. Patogeneticheskaja terapija sostojanij gipoksii organov i tkanej na kletochnom urovne. Lechaschi Vrach Journal. 2017;7:11. (In Russ.). https://www.lvrach.ru/2017/07/15436757</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Зуева И.Б., Ким Ю.В. Применение цитохрома C в реальной клинической практике на современном этапе. Современная медицина. 2019;4(16):22-26 http://infocom-pany-sovmed.ru/wp-content/uploads/2020/02/18-22.pdf</mixed-citation><mixed-citation xml:lang="en">Zueva IB, Kim YuV. Application of cytochrome C in real clinical practice at the present stage. Sovremennaja medicina. 2019;4(16):22-26. (In Russ.). http://infocom-pany-sovmed.ru/wp-content/uploads/2020/02/18-22.pdf</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Borea PA, Gessi S, Merighi S, Varani K. Adenosine as a Multi-Signalling Guardian Angel in Human Diseases: When, Where and How Does it Exert its Protective Effects? Trends Pharmacol Sci. 2016;37(6):419-434. https://doi.org/10.1016/j.tips.2016.02.006</mixed-citation><mixed-citation xml:lang="en">Borea PA, Gessi S, Merighi S, Varani K. Adenosine as a Multi-Signalling Guardian Angel in Human Diseases: When, Where and How Does it Exert its Protective Effects? Trends Pharmacol Sci. 2016;37(6):419-434. https://doi.org/10.1016/j.tips.2016.02.006</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Burnstock G. Purinergic Signaling in the Cardiovascular System. Circ Res. 2017;120(1):207-228. https://doi.org/10.1161/CIRCRESAHA.116.309726</mixed-citation><mixed-citation xml:lang="en">Burnstock G. Purinergic Signaling in the Cardiovascular System. Circ Res. 2017;120(1):207-228. https://doi.org/10.1161/CIRCRESAHA.116.309726</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Rork TH, Wallace KL, Kennedy DP, Marshall MA, Lankford AR, Linden J. Adenosine A2A receptor activation reduces infarct size in the isolated, perfused mouse heart by inhibiting resident cardiac mast cell degranulation. Am J Physiol Heart Circ Physiol. 2008;295(5):H1825-1833. https://doi.org/10.1152/ajpheart.495.2008</mixed-citation><mixed-citation xml:lang="en">Rork TH, Wallace KL, Kennedy DP, Marshall MA, Lankford AR, Linden J. Adenosine A2A receptor activation reduces infarct size in the isolated, perfused mouse heart by inhibiting resident cardiac mast cell degranulation. Am J Physiol Heart Circ Physiol. 2008;295(5):H1825-1833. https://doi.org/10.1152/ajpheart.495.2008</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">McIntosh VJ, Lasley RD. Adenosine receptor-mediated cardioprotection: are all 4 subtypes required or redundant? J Cardiovasc Pharmacol Ther. 2012;17(1):21-33. https://doi.org/10.1177/1074248410396877</mixed-citation><mixed-citation xml:lang="en">McIntosh VJ, Lasley RD. Adenosine receptor-mediated cardioprotection: are all 4 subtypes required or redundant? J Cardiovasc Pharmacol Ther. 2012;17(1):21-33. https://doi.org/10.1177/1074248410396877</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Mahaffey KW, Puma JA, Barbagelata NA, DiCarli MF, Leesar MA, Browne KF, Eisenberg PR, Bolli R, Casas AC, Molina-Viamonte V, Orlandi C, Blevins R, Gibbons RJ, Califf RM, Granger CB. Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial. J Am Coll Cardiol. 1999;34(6):1711- 1720. https://doi.org/10.1016/s0735-1097(99)00418-0</mixed-citation><mixed-citation xml:lang="en">Mahaffey KW, Puma JA, Barbagelata NA, DiCarli MF, Leesar MA, Browne KF, Eisenberg PR, Bolli R, Casas AC, Molina-Viamonte V, Orlandi C, Blevins R, Gibbons RJ, Califf RM, Granger CB. Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial. J Am Coll Cardiol. 1999;34(6):1711- 1720. https://doi.org/10.1016/s0735-1097(99)00418-0</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Ross AM, Gibbons RJ, Stone GW, Kloner RA, Alexander RW; AMISTAD-II Investigators. A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II). J Am Coll Cardiol. 2005;45(11):1775-1780. https://doi.org/10.1016/j.jacc.2005.02.061</mixed-citation><mixed-citation xml:lang="en">Ross AM, Gibbons RJ, Stone GW, Kloner RA, Alexander RW; AMISTAD-II Investigators. A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II). J Am Coll Cardiol. 2005;45(11):1775-1780. https://doi.org/10.1016/j.jacc.2005.02.061</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Kloner RA, Forman MB, Gibbons RJ, Ross AM, Alexander RW, Stone GW. Impact of time to therapy and reperfusion modality on the effcacy of adenosine in acute myocardial infarction: the AMISTAD-2 trial. Eur Heart J. 2006;27(20):2400-2405. https://doi.org/10.1093/eurheartj/ehl094</mixed-citation><mixed-citation xml:lang="en">Kloner RA, Forman MB, Gibbons RJ, Ross AM, Alexander RW, Stone GW. Impact of time to therapy and reperfusion modality on the effcacy of adenosine in acute myocardial infarction: the AMISTAD-2 trial. Eur Heart J. 2006;27(20):2400-2405. https://doi.org/10.1093/eurheartj/ehl094</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Su Q, Nyi TS, Li L. Adenosine and verapamil for norefow during primary percutaneous coronary intervention in people with acute myocardial infarction. Cochrane Database Syst Rev. 2015;(5):CD009503. https://doi.org/10.1002/14651858.CD009503.pub3</mixed-citation><mixed-citation xml:lang="en">Su Q, Nyi TS, Li L. Adenosine and verapamil for norefow during primary percutaneous coronary intervention in people with acute myocardial infarction. Cochrane Database Syst Rev. 2015;(5):CD009503. https://doi.org/10.1002/14651858.CD009503.pub3</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Bulluck H, Sirker A, Loke YK, Garcia-Dorado D, Hausenloy DJ. Clinical beneft of adenosine as an adjunct to reperfusion in ST-elevation myocardial infarction patients: An updated meta-analysis of randomized controlled trials. Int J Cardiol. 2016;202:228-237. https://doi.org/10.1016/j.ijcard.2015.09.005</mixed-citation><mixed-citation xml:lang="en">Bulluck H, Sirker A, Loke YK, Garcia-Dorado D, Hausenloy DJ. Clinical beneft of adenosine as an adjunct to reperfusion in ST-elevation myocardial infarction patients: An updated meta-analysis of randomized controlled trials. Int J Cardiol. 2016;202:228-237. https://doi.org/10.1016/j.ijcard.2015.09.005</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Lopaschuk GD, Ussher JR, Folmes CD, Jaswal JS, Stanley WC. Myocardial fatty acid metabolism in health and disease. Physiol Rev. 2010;90(1):207-258. https://doi.org/10.1152/physrev.00015.2009</mixed-citation><mixed-citation xml:lang="en">Lopaschuk GD, Ussher JR, Folmes CD, Jaswal JS, Stanley WC. Myocardial fatty acid metabolism in health and disease. Physiol Rev. 2010;90(1):207-258. https://doi.org/10.1152/physrev.00015.2009</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Олейников Д.А., Яшин А.В. Энергетический обмен миокарда в норме и при патологии. РВЖ МДЖ. 2015;5:38-41 http://cyberleninka.ru/article/n/energeticheskiy-obmen-miokarda-v-norme-i-pri-patologii#</mixed-citation><mixed-citation xml:lang="en">Oleynikov DA, Yashin AV. Energy metabolism in normal and failing myocardium. RVJ SWA. 2015;5:38-41. (In Russ.). http://cyberleninka.ru/article/n/energeticheskiy-obmen-miokarda-v-norme-i-pri-patologii#</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Díaz R, Goyal A, Mehta SR, Afzal R, Xavier D, Pais P, Chrolavicius S, Zhu J, Kazmi K, Liu L, Budaj A, Zubaid M, Avezum A, Ruda M, Yusuf S. Glucose-insulin-potassium therapy in patients with ST-segment elevation myocardial infarction. JAMA. 2007;298(20):2399-2405. https://doi.org/10.1001/jama.298.20.2399</mixed-citation><mixed-citation xml:lang="en">Díaz R, Goyal A, Mehta SR, Afzal R, Xavier D, Pais P, Chrolavicius S, Zhu J, Kazmi K, Liu L, Budaj A, Zubaid M, Avezum A, Ruda M, Yusuf S. Glucose-insulin-potassium therapy in patients with ST-segment elevation myocardial infarction. JAMA. 2007;298(20):2399-2405. https://doi.org/10.1001/jama.298.20.2399</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Danilenko LM, Klochkova GN, Kizilova IV, Korokin MV. Metabolic cardioprotection: new concepts in implementation of cardioprotective effects of meldonium. Research result: pharmacology and clinical pharmacology. 2016;2(3):95-100. https://doi.org/10.18413/2500-235X-2016-2-3-95-100</mixed-citation><mixed-citation xml:lang="en">Danilenko LM, Klochkova GN, Kizilova IV, Korokin MV. Metabolic cardioprotection: new concepts in implementation of cardioprotective effects of meldonium. Research result: pharmacology and clinical pharmacology. 2016;2(3):95-100. https://doi.org/10.18413/2500-235X-2016-2-3-95-100</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Асташкин Е.И., Глезер М.Г. Роль L-карнитина в энергетическом обмене кардиомиоцитов и лечении заболеваний сердечно-сосудистой системы. Кардиология и сердечно-сосудистая хирургия. 2012;5(6):58-65 https://www.mediasphera.ru/issues/kardiologiya-i-serdechno-sosudistayakhirurgiya/2012/6/031996-63852012611</mixed-citation><mixed-citation xml:lang="en">Astashkin EI, Glezer MG. The role of L-carnitine in the energetic metabolism of cardiomyocytes and treatment of cardio-vascular diseases. Russian Journal of Cardiology and Cardiovascular Surgery. 2012;5(6):58-65. (In Russ.). https://www.mediasphera.ru/issues/kardiologiya-i-serdechno-sosudistayakhirurgiya/2012/6/031996-63852012611</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Аронов Д.М. Реалии и перспективы применения l-карнитина в кардиологии. Российский кардиологический журнал. 2013;(5):73-80 https://doi.org/10.15829/1560-4071-2013-5-73-80</mixed-citation><mixed-citation xml:lang="en">Aronov DM. L-carnitine in cardiology: reality and perspectives. Russian Journal of Cardiology. 2013;(5):73-80. (In Russ.). https://doi.org/10.15829/1560-4071-2013-5-73-80</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Асташкин Е.И., Глезер М.Г. Влияние L-карнитина на оксидативный стресс при сердечно-сосудистых заболеваниях. Медицинский Совет. 2016;(10):104-110 https://doi.org/10.21518/2079-701X-2016-10-104-110</mixed-citation><mixed-citation xml:lang="en">Astashkin EI, Glezer MG. Effect of L-carnitine on oxydative stress at cardiovascular diseases. Medical Council. 2016;(10):104-110. (In Russ.). https://doi.org/10.21518/2079-701X-2016-10-104-110</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Davini P, Bigalli A, Lamanna F, Boem A. Controlled study on L-carnitine therapeutic effcacy in post-infarction. Drugs Exp Clin Res. 1992;18(8):355-365. PMID: 1292918</mixed-citation><mixed-citation xml:lang="en">Davini P, Bigalli A, Lamanna F, Boem A. Controlled study on L-carnitine therapeutic effcacy in post-infarction. Drugs Exp Clin Res. 1992;18(8):355-365. PMID: 1292918</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Dinicolantonio JJ, Niazi AK, McCarty MF, Lavie CJ, Liberopoulos E, O'Keefe JH. L-carnitine for the treatment of acute myocardial infarction. Rev Cardiovasc Med. 2014;15(1):52-62. PMID: 24762466</mixed-citation><mixed-citation xml:lang="en">Dinicolantonio JJ, Niazi AK, McCarty MF, Lavie CJ, Liberopoulos E, O'Keefe JH. L-carnitine for the treatment of acute myocardial infarction. Rev Cardiovasc Med. 2014;15(1):52-62. PMID: 24762466</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Сизова Ж.М., Ших Е.В., Махова А.А. Применение L-карнитина в общей врачебной практике. Терапевтический архив. 2019;91(1):114-120 https://doi.org/10.26442/00403660.2019.01.000040</mixed-citation><mixed-citation xml:lang="en">Sizova ZM, Shikh EV, Makhova AA. Signifcance of L-carnitine in internal medicine. Therapeutic archive. 2019;91(1):114-120 (In Russ.). https://doi.org/10.26442/00403660.2019.01.000040</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">De Pasquale B, Righetti G, Menotti A. La L-carnitina nella terapia dell'infarto miocardico acuto [L-carnitine for the treatment of acute myocardial infarct]. Cardiologia. 1990;35(7):591-596. PMID: 2088604</mixed-citation><mixed-citation xml:lang="en">De Pasquale B, Righetti G, Menotti A. La L-carnitina nella terapia dell'infarto miocardico acuto [L-carnitine for the treatment of acute myocardial infarct]. Cardiologia. 1990;35(7):591-596. PMID: 2088604</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Rizos I. Three-year survival of patients with heart failure caused by dilated cardiomyopathy and L-carnitine administration. Am Heart J. 2000;139(2 Pt3):S120-S123. https://doi.org/10.1067/mhj.2000.103917</mixed-citation><mixed-citation xml:lang="en">Rizos I. Three-year survival of patients with heart failure caused by dilated cardiomyopathy and L-carnitine administration. Am Heart J. 2000;139(2 Pt3):S120-S123. https://doi.org/10.1067/mhj.2000.103917</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Tarantini G, Scrutinio D, Bruzzi P, Boni L, Rizzon P, Iliceto S. Metabolic treatment with L-carnitine in acute anterior ST segment elevation myocardial infarction. A randomized controlled trial. Cardiology. 2006;106(4):215-223. https://doi.org/10.1159/000093131</mixed-citation><mixed-citation xml:lang="en">Tarantini G, Scrutinio D, Bruzzi P, Boni L, Rizzon P, Iliceto S. Metabolic treatment with L-carnitine in acute anterior ST segment elevation myocardial infarction. A randomized controlled trial. Cardiology. 2006;106(4):215-223. https://doi.org/10.1159/000093131</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">DiNicolantonio JJ, Lavie CJ, Fares H, Menezes AR, O'Keefe JH. L-carnitine in the secondary prevention of cardiovascular disease: systematic review and meta-analysis. Mayo Clin Proc. 2013;88(6):544-551. https://doi.org/10.1016/j.mayocp.2013.02.007</mixed-citation><mixed-citation xml:lang="en">DiNicolantonio JJ, Lavie CJ, Fares H, Menezes AR, O'Keefe JH. L-carnitine in the secondary prevention of cardiovascular disease: systematic review and meta-analysis. Mayo Clin Proc. 2013;88(6):544-551. https://doi.org/10.1016/j.mayocp.2013.02.007</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Thompson WG, Hensrud DD, Murad MH. Regarding L-Carnitine and Cardiovascular Disease. Letter To The Editor. Mayo Clin Proc. 2013;88(8):899-900. https://doi.org/10.1016/j.mayocp.2013.06.011</mixed-citation><mixed-citation xml:lang="en">Thompson WG, Hensrud DD, Murad MH. Regarding L-Carnitine and Cardiovascular Disease. Letter To The Editor. Mayo Clin Proc. 2013;88(8):899-900. https://doi.org/10.1016/j.mayocp.2013.06.011</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Song X, Qu H, Yang Z, Rong J, Cai W, Zhou H. Effcacy and Safety of L-Carnitine Treatment for Chronic Heart Failure: A Meta-Analysis of Randomized Controlled Trials. Biomed Res Int. 2017;2017:6274854. https://doi.org/10.1155/2017/6274854</mixed-citation><mixed-citation xml:lang="en">Song X, Qu H, Yang Z, Rong J, Cai W, Zhou H. Effcacy and Safety of L-Carnitine Treatment for Chronic Heart Failure: A Meta-Analysis of Randomized Controlled Trials. Biomed Res Int. 2017;2017:6274854. https://doi.org/10.1155/2017/6274854</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Стаценко М.Е., Туркина С.В., Ермоленко А.А. Нерешенные вопросы цитопротективной терапии у пациентов с ишемической болезнью сердца. Терапевтический архив. 2015;87(12):101-106 https://doi.org/10.17116/terarkh20158712101-106</mixed-citation><mixed-citation xml:lang="en">Statsenko ME, Turkina SV, Ermolenko AA. Unsolved problems of cytoprotective therapy in patients with coronary heart disease. Therapeutic archive. 2015;87(12):101-106. (In Russ.). https://doi.org/10.17116/terarkh20158712101-106</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Гороховская Г.Н., Васюк Ю.А., Мартынов А.И., Майчук Е.Ю., Юн В.Л., Трутень И.В., Петина М.М. Современные возможности применения нитропрепаратов у больных с ишемической болезнью сердца: от стенокардии до полиморбидности. Consilium Medicum. 2018;12:61-68 https://doi.org/10.26442/20751753.2018.12.180063</mixed-citation><mixed-citation xml:lang="en">Gorokhovskaya GN, Vasyuk YuA, Martynov AI, Maychuk EYu, Yun VL, Truten IV, Petina MM. Modern opportunities of nitropreparations in patients with ischemic heart disease:from angina to polymorbidity. Consilium Medicum. 2018;20(12):61-68. (In Russ.). https://doi.org/10.26442/20751753.2018.12.180063</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Перепеч Н.Б. Метаболические миокардиальные цитопротекторы в терапии стабильной ишемической болезни сердца: доказательства эффективности и рекомендации по применению. Медицинский Совет. 2017;(12):36-48 https://doi.org/10.21518/2079-701X-2017-12-36-48</mixed-citation><mixed-citation xml:lang="en">Perepech NB. Metabolic myocardial cytoprotectors in therapy of stable ischemic heart disease: evidence of effectiveness and use recommendations. Medical Council. 2017;(12):36-48. (In Russ.). https://doi.org/10.21518/2079-701X-2017-12-36-48</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Balla C, Pavasini R, Ferrari R. Treatment of Angina: Where Are We? Cardiology. 2018;140(1):52-67. https://doi.org/10.1159/000487936</mixed-citation><mixed-citation xml:lang="en">Balla C, Pavasini R, Ferrari R. Treatment of Angina: Where Are We? Cardiology. 2018;140(1):52-67. https://doi.org/10.1159/000487936</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">Marzilli M, Vinereanu D, Lopaschuk G, Chen Y., Dalal JJ, Danchin N, Etriby E, Ferrari R, Gowdak LH, Lopatin Y, Milicic D, Parkhomenko A, Pinto F, Ponikowski P, Seferovic P, Rosano GMC. Trimetazidine in cardiovascular medicine. Int J Cardiol. 2019;293:39-44. https://doi.org/10.1016/j.ijcard.2019.05.063</mixed-citation><mixed-citation xml:lang="en">Marzilli M, Vinereanu D, Lopaschuk G, Chen Y., Dalal JJ, Danchin N, Etriby E, Ferrari R, Gowdak LH, Lopatin Y, Milicic D, Parkhomenko A, Pinto F, Ponikowski P, Seferovic P, Rosano GMC. Trimetazidine in cardiovascular medicine. Int J Cardiol. 2019;293:39-44. https://doi.org/10.1016/j.ijcard.2019.05.063</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Ciapponi A, Pizarro R, Harrison J. Trimetazidine for stable angina. Cochrane Database Syst Rev. 2017;3(3):CD003614. https://doi.org/10.1002/14651858.CD003614.pub3</mixed-citation><mixed-citation xml:lang="en">Ciapponi A, Pizarro R, Harrison J. Trimetazidine for stable angina. Cochrane Database Syst Rev. 2017;3(3):CD003614. https://doi.org/10.1002/14651858.CD003614.pub3</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">Peng S, Zhao M, Wan J, Fang Q, Fang D, Li K. The effcacy of trimetazidine on stable angina pectoris: a meta-analysis of randomized clinical trials. Int J Cardiol. 2014;177(3):780-785. https://doi.org/10.1016/j.ijcard.2014.10.149</mixed-citation><mixed-citation xml:lang="en">Peng S, Zhao M, Wan J, Fang Q, Fang D, Li K. The effcacy of trimetazidine on stable angina pectoris: a meta-analysis of randomized clinical trials. Int J Cardiol. 2014;177(3):780-785. https://doi.org/10.1016/j.ijcard.2014.10.149</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Iyengar SS, Rosano GM. Effect of antianginal drugs in stable angina on predicted mortality risk after surviving a myocardial infarction: a preliminary study (METRO). Am J Cardiovasc Drugs. 2009;9(5):293-297. https://doi.org/10.2165/11316840-000000000-00000</mixed-citation><mixed-citation xml:lang="en">Iyengar SS, Rosano GM. Effect of antianginal drugs in stable angina on predicted mortality risk after surviving a myocardial infarction: a preliminary study (METRO). Am J Cardiovasc Drugs. 2009;9(5):293-297. https://doi.org/10.2165/11316840-000000000-00000</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Effect of 48-h intravenous trimetazidine on short- and long-term outcomes of patients with acute myocardial infarction, with and without thrombolytic therapy; A double-blind, placebo-controlled, randomized trial. The EMIP-FR Group. European Myocardial Infarction Project--Free Radicals. Eur Heart J. 2000;21(18):1537- 1546. https://doi.org/10.1053/euhj.1999.2439</mixed-citation><mixed-citation xml:lang="en">Effect of 48-h intravenous trimetazidine on short- and long-term outcomes of patients with acute myocardial infarction, with and without thrombolytic therapy; A double-blind, placebo-controlled, randomized trial. The EMIP-FR Group. European Myocardial Infarction Project--Free Radicals. Eur Heart J. 2000;21(18):1537- 1546. https://doi.org/10.1053/euhj.1999.2439</mixed-citation></citation-alternatives></ref><ref id="cit57"><label>57</label><citation-alternatives><mixed-citation xml:lang="ru">Gao D, Ning N, Niu X, Hao G, Meng Z. Trimetazidine: a metaanalysis of randomised controlled trials in heart failure. Heart. 2011;97(4):278-286. https://doi.org/10.1136/hrt.2010.208751</mixed-citation><mixed-citation xml:lang="en">Gao D, Ning N, Niu X, Hao G, Meng Z. Trimetazidine: a metaanalysis of randomised controlled trials in heart failure. Heart. 2011;97(4):278-286. https://doi.org/10.1136/hrt.2010.208751</mixed-citation></citation-alternatives></ref><ref id="cit58"><label>58</label><citation-alternatives><mixed-citation xml:lang="ru">Zhou X, Chen J. Is treatment with trimetazidine benefcial in patients with chronic heart failure? PLoS One. 2014;9(5):e94660. https://doi.org/10.1371/journal.pone.0094660</mixed-citation><mixed-citation xml:lang="en">Zhou X, Chen J. Is treatment with trimetazidine benefcial in patients with chronic heart failure? PLoS One. 2014;9(5):e94660. https://doi.org/10.1371/journal.pone.0094660</mixed-citation></citation-alternatives></ref><ref id="cit59"><label>59</label><citation-alternatives><mixed-citation xml:lang="ru">Dzerve V, MILSS I Study Group. A dose-dependent improvement in exercise tolerance in patients with stable angina treated with mildronate: a clinical trial "MILSS I". Medicina (Kaunas). 2011;47(10):544-551. PMID: 22186118. https://pubmed.ncbi.nlm.nih.gov/22186118/</mixed-citation><mixed-citation xml:lang="en">Dzerve V, MILSS I Study Group. A dose-dependent improvement in exercise tolerance in patients with stable angina treated with mildronate: a clinical trial "MILSS I". Medicina (Kaunas). 2011;47(10):544-551. PMID: 22186118. https://pubmed.ncbi.nlm.nih.gov/22186118/</mixed-citation></citation-alternatives></ref><ref id="cit60"><label>60</label><citation-alternatives><mixed-citation xml:lang="ru">Гороховская Г.Н., Юн В.Л., Скотников А.С., Мартынов А.И., Майчук Е.Ю. Эффективность применения мельдония у больных с хронической сердечной недостаточностью. Медицинский совет. 2017;(12):118-122 https://doi.org/10.21518/2079-701X-2017-12-118-122</mixed-citation><mixed-citation xml:lang="en">Gorokhovskaya GN, Yoon VL, Skotnikov AS, Martynov AI, Maychuk EYu. Effectiveness of meldoniumin in chronic heart failure patients. Medical Council. 2017;(12):118-122. (In Russ.). https://doi.org/10.21518/2079-701X-2017-12-118-122</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>
