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Стабильная ишемическая болезнь сердца. На пороге пересмотра тактики ведения и классификации – мы ждем перемен. Разбор клинических случаев
Адашева Т.В., Саморукова Е.И., Ахмедярова Л.Б., Одинцова Д.В. Стабильная ишемическая болезнь сердца. На пороге пересмотра тактики ведения и классификации – мы ждем перемен. Разбор клинических случаев. Consilium Medicum. 2019; 21 (10): 20–26. DOI: 10.26442/20751753.2019.10.190545
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Adasheva T.V., Samorukova E.I., Akhmedyarova L.B., Odintsova D.V. Stable ischemic heart disease. A revision of management and classification. We are waiting for changes. Clinical cases. Consilium Medicum. 2019; 21 (10): 20–26. DOI: 10.26442/20751753.2019.10.190545
Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.
Аннотация
В статье обсуждаются планирующиеся изменения в подходах к классификации и терапии стабильной ишемической болезни сердца (ИБС). Приводятся последние экспертные консенсусы, метаанализы, обосновывающие основные положения персонализации симптоматической терапии стабильной стенокардии с выбором антиангинальных лекарственных средств в зависимости от клинического и патофизиологического фенотипов больного. Обсуждается патофизиология влияния сердечного ритма на миокардиальную ишемию и контрактильность. Увеличение частоты сердечных сокращений приводит к уменьшению продолжительности диастолы и редукции коллатерального кровотока в условиях обструктивного поражения коронарного русла. Анализируются механизмы взаимодействия между миокардиальной ишемией и контрактильной функцией – формирование преходящей контрактильной дисфункции, затем гибернированного миокарда и при повторяющихся эпизодах ишемии – гибель кардиомиоцитов и развитие непреходящей контрактильной дисфункции. Описываются клинические случаи модификации терапии стабильной ИБС в зависимости от клинического фенотипа пациента: стабильная ИБС с гиперактивацией симпатической нервной системы и декомпенсация сердечной недостаточности у пациента с ИБС при неадекватном контроле ритма. Обсуждается современная тактика терапии для контроля ритма (β-адреноблокаторы, ингибитор if-каналов ивабрадин, антагонисты кальция) и использование фиксированных комбинаций (β-адреноблокатор + ингибитор if-каналов).
Ключевые слова: стабильная ишемическая болезнь сердца, антиангинальные препараты, фиксированные комбинации, персонализация фармакотерапии.
Ключевые слова: стабильная ишемическая болезнь сердца, антиангинальные препараты, фиксированные комбинации, персонализация фармакотерапии.
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The article discusses the main principles of approaching the personalization of stable angina symptomatic therapy with a rationale for the choice of antianginal medications depending on clinical and pathophysiological phenotypes of the patient. This article summarizes the determinants and control of coronary blood flow and heart rate influence. Increased heart rate reduces the duration of diastole and thus coronary blood flow when metabolic vasodilation is no longer able to increase coronary blood flow. Increased heart rate also reduces the collateral blood flow. Association myocardial ischemia and myocardial contractile function is analyzed: reversible ischemic contractile dysfunction, myocardial hibernation, irreversible loss of regional contractile function. The clinical cases and the treatment modification according clinical phenotypes of the patient (stable ischemic heart disease with sympathetic activation and stable ischemic heart disease with heart failure decompensation) are discussed. Aspects of monotherapy and combined therapy for heart rate control and use of fixed combinations of antianginal medications are presented.
Key words: stable ischemic heart disease, antianginal medications, fixed combinations, pharmacotherapy personalization.
Key words: stable ischemic heart disease, antianginal medications, fixed combinations, pharmacotherapy personalization.
Полный текст
Список литературы
1. Montalescot G, Sechtem U, Achenbach S et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013; 34 (38): 2949–3003.
2. Ferrari R, Camici PG, Crea F et al. Expert consensus document: a “diamond” approach to personalized treatment of angina. Nat Rev Cardiol 2018; 15 (2): 120–32.
3. Ferrari R, Pavasini R, Camici PG et al. Anti-anginal drugs–beliefs and evidence: systematic review covering 50 years of medical treatment. Eur Heart J 2019; 40 (2): 190–4. DOI: doi/10.1093/eurheartj/ehy504/5084899
4. Balla С, Pavasini К, Ferrari R. Treatment of Angina: Where Are We? Cardiology 2018; 140: 52–67. DOI: 10.1159/000487936
5. Laskey et al. Discharge Heart Rate and Outcomes in Heart Failure. J Am Heart Assoc 2015; 4: e001626. DOI: 10.1161/JAHA.114.001626
6. Heusch G. Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: benefit from selective bradycardic agents. Br J Pharmacol 2008; 153: 1589–601.
7. Bassenge E, Heusch G. Endothelial and neuro-humoral control of coronary blood flow in health and disease. Rev Physiol Biochem Pharmacol 1990; 116: 77–165.
8. Traupe T, Gloekler S, de Marchi SF et al. Assessment of the human coronary collateral circulation. Circulation 2010; 122: 1210–20.
9. Heusch G, Yoshimoto N. Effects of heart rate and perfusion pressure on segmental coronary resistances and collateral perfusion. Pflügers Arch 1983; 397: 284–9.
10. Heusch G. Myocardial ischemia: Lack of coronary blood flow or myocardial oxygen supply/ demand imbalance? Circ Res 2016; 119: 194–6.
11. Heusch G. The regional myocardial flow-function relationship: a framework for an understanding of acute ischemia, hibernation, stunning and coronary microembolization. Circ Res 2013; 112: 1535–7.
12. Levy BI, Heusch G, Camici PG. The many faces of myocardial ischemia and angina. Cardiovascular Res 2019; 115: 1460–70. DOI: doi/10.1093/cvr/cvz160/5522026
13. Custodis F, Schirmer SH, Baumhäkel M et al. Vascular pathophysiology in response to increased heart rate. J Am Coll Cardiol 2010; 56: 1973–83.
14. Monnet X, Ghaleh B, Colin P et al. Effects of heart rate reduction with ivabradine on exercise induced myocardial ischemia and stunning. J Pharmacol Exp Ther 2001; 299: 1133–9.
15. Heusch G, Skyschally A, Gres P et al. Improvement of regional myocardial blood flow and function and reduction of infarct size with ivabradine: protection beyond heart rate reduction. Eur Heart J 2008; 29: 2265–75.
16. Gloekler S, Traupe T, Stoller M et al. The effect of heart rate reduction by ivabradine on collateral function in patients with chronic stable coronary artery disease. Heart 2014; 100: 160–6.
17. Monnet X, Colin P, Ghaleh B et al. Heart rate reduction during exercise-induced myocardial ischaemia and stunning. Eur Heart J 2004; 25: 579–86.
18. Maranta F, Tondi L, Agricola E et al. Ivabradine reduces myocardial stunning in patients with exercise-inducible ischaemia. Basic Res Cardiol 2015; 110: 55.
19. Kleinbongard P, Gedik N, Witting P et al. Pleiotropic, heart rate-independent cardioprotection by ivabradine. Br J Pharmacol 2015; 172: 43804390.
20. Heusch G, Kleinbongard P. Ivabradine: Cardioprotection By and Beyond Heart Rate Reduction. Drugs 2016; 76: 733–40.
21. Fox K, Ford I, Steg PJ et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomized, double-blind, placebo-controlled trial. Lancet 2008; 372: 807–16.
22. Fox K, Ford I, Steg PJ et al. Relationship between Ivabradine treatment and cardiovascular outcomes in patients with stable coronary artery disease and left-ventricular systolic dysfunction with limiting angina: a subgroup analysis of the randomized, controlled BEAUTIFUL trial. Eur Heart J 2009; 30: 2337–45.
23. Tardif JC, Ponikowski P, Kahan T; ASSOCIATE Study Investigators. Efficacy of the I(f) current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4-month, randomized, placebo-controlled trial. Eur Heart J 2009; 30 (5): 540–8.
24. Tardif JC, Ponikowski P, Kahan T; ASSOCIATE Study Investigators. Effects of ivabradine in patients with stable angina receiving -blockers according to baseline heart rate: an analysis of the ASSOCIATE study. Int J Cardiol 2013; 168 (2): 789–94.
25. Amosova E, Andrejev E, Zaderey I et al. Efficacy of ivabradine in combination with Betablocker versus uptitration of Beta-blocker in patients with stable angina. Cardiovasc Drugs Ther 2011; 25 (6): 531–7.
26. Williams B, Mancia G, Spiering W et al. 2018 ESC/ESH 2013 ESC guidelines for the management of arterial hypertension: the Task Force on the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur Heart J 2018; 00: 1–98. DOI: 10.1093/eurheartj/ehy339
27. Qiu S, Cai X, Sun Z et al. Heart Rate Recovery and Risk of Cardiovascular Events and All-CauseMortality: A Meta-Analysis of Prospective Cohort Studies. J Am Heart Assoc 2017; 6:e005505. DOI: 10.1161/JAHA.117.005505
28. Divchev D, Stöckl G; study investigators. Treatment of Stable Angina with a New FixedDose Combination of Ivabradine and Metoprolol: Effectiveness and Tolerability in Routine Clinical Practice. Cardiol Ther 2017; 6 (2): 239–49.
29. Kaski JC, Crea F, Gersh BJ, Camici PG. Reappraisal of Ischemic Heart Disease: Fundamental Role of Coronary Microvascular Dysfunction in the Pathogenesis of Angina Pectoris. Circulation 2018; 138: 1463–80.
2. Ferrari R, Camici PG, Crea F et al. Expert consensus document: a “diamond” approach to personalized treatment of angina. Nat Rev Cardiol 2018; 15 (2): 120–32.
3. Ferrari R, Pavasini R, Camici PG et al. Anti-anginal drugs–beliefs and evidence: systematic review covering 50 years of medical treatment. Eur Heart J 2019; 40 (2): 190–4. DOI: doi/10.1093/eurheartj/ehy504/5084899
4. Balla С, Pavasini К, Ferrari R. Treatment of Angina: Where Are We? Cardiology 2018; 140: 52–67. DOI: 10.1159/000487936
5. Laskey et al. Discharge Heart Rate and Outcomes in Heart Failure. J Am Heart Assoc 2015; 4: e001626. DOI: 10.1161/JAHA.114.001626
6. Heusch G. Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: benefit from selective bradycardic agents. Br J Pharmacol 2008; 153: 1589–601.
7. Bassenge E, Heusch G. Endothelial and neuro-humoral control of coronary blood flow in health and disease. Rev Physiol Biochem Pharmacol 1990; 116: 77–165.
8. Traupe T, Gloekler S, de Marchi SF et al. Assessment of the human coronary collateral circulation. Circulation 2010; 122: 1210–20.
9. Heusch G, Yoshimoto N. Effects of heart rate and perfusion pressure on segmental coronary resistances and collateral perfusion. Pflügers Arch 1983; 397: 284–9.
10. Heusch G. Myocardial ischemia: Lack of coronary blood flow or myocardial oxygen supply/ demand imbalance? Circ Res 2016; 119: 194–6.
11. Heusch G. The regional myocardial flow-function relationship: a framework for an understanding of acute ischemia, hibernation, stunning and coronary microembolization. Circ Res 2013; 112: 1535–7.
12. Levy BI, Heusch G, Camici PG. The many faces of myocardial ischemia and angina. Cardiovascular Res 2019; 115: 1460–70. DOI: doi/10.1093/cvr/cvz160/5522026
13. Custodis F, Schirmer SH, Baumhäkel M et al. Vascular pathophysiology in response to increased heart rate. J Am Coll Cardiol 2010; 56: 1973–83.
14. Monnet X, Ghaleh B, Colin P et al. Effects of heart rate reduction with ivabradine on exercise induced myocardial ischemia and stunning. J Pharmacol Exp Ther 2001; 299: 1133–9.
15. Heusch G, Skyschally A, Gres P et al. Improvement of regional myocardial blood flow and function and reduction of infarct size with ivabradine: protection beyond heart rate reduction. Eur Heart J 2008; 29: 2265–75.
16. Gloekler S, Traupe T, Stoller M et al. The effect of heart rate reduction by ivabradine on collateral function in patients with chronic stable coronary artery disease. Heart 2014; 100: 160–6.
17. Monnet X, Colin P, Ghaleh B et al. Heart rate reduction during exercise-induced myocardial ischaemia and stunning. Eur Heart J 2004; 25: 579–86.
18. Maranta F, Tondi L, Agricola E et al. Ivabradine reduces myocardial stunning in patients with exercise-inducible ischaemia. Basic Res Cardiol 2015; 110: 55.
19. Kleinbongard P, Gedik N, Witting P et al. Pleiotropic, heart rate-independent cardioprotection by ivabradine. Br J Pharmacol 2015; 172: 43804390.
20. Heusch G, Kleinbongard P. Ivabradine: Cardioprotection By and Beyond Heart Rate Reduction. Drugs 2016; 76: 733–40.
21. Fox K, Ford I, Steg PJ et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomized, double-blind, placebo-controlled trial. Lancet 2008; 372: 807–16.
22. Fox K, Ford I, Steg PJ et al. Relationship between Ivabradine treatment and cardiovascular outcomes in patients with stable coronary artery disease and left-ventricular systolic dysfunction with limiting angina: a subgroup analysis of the randomized, controlled BEAUTIFUL trial. Eur Heart J 2009; 30: 2337–45.
23. Tardif JC, Ponikowski P, Kahan T; ASSOCIATE Study Investigators. Efficacy of the I(f) current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4-month, randomized, placebo-controlled trial. Eur Heart J 2009; 30 (5): 540–8.
24. Tardif JC, Ponikowski P, Kahan T; ASSOCIATE Study Investigators. Effects of ivabradine in patients with stable angina receiving -blockers according to baseline heart rate: an analysis of the ASSOCIATE study. Int J Cardiol 2013; 168 (2): 789–94.
25. Amosova E, Andrejev E, Zaderey I et al. Efficacy of ivabradine in combination with Betablocker versus uptitration of Beta-blocker in patients with stable angina. Cardiovasc Drugs Ther 2011; 25 (6): 531–7.
26. Williams B, Mancia G, Spiering W et al. 2018 ESC/ESH 2013 ESC guidelines for the management of arterial hypertension: the Task Force on the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur Heart J 2018; 00: 1–98. DOI: 10.1093/eurheartj/ehy339
27. Qiu S, Cai X, Sun Z et al. Heart Rate Recovery and Risk of Cardiovascular Events and All-CauseMortality: A Meta-Analysis of Prospective Cohort Studies. J Am Heart Assoc 2017; 6:e005505. DOI: 10.1161/JAHA.117.005505
28. Divchev D, Stöckl G; study investigators. Treatment of Stable Angina with a New FixedDose Combination of Ivabradine and Metoprolol: Effectiveness and Tolerability in Routine Clinical Practice. Cardiol Ther 2017; 6 (2): 239–49.
29. Kaski JC, Crea F, Gersh BJ, Camici PG. Reappraisal of Ischemic Heart Disease: Fundamental Role of Coronary Microvascular Dysfunction in the Pathogenesis of Angina Pectoris. Circulation 2018; 138: 1463–80.
________________________________________________
1. Montalescot G, Sechtem U, Achenbach S et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013; 34 (38): 2949–3003.
2. Ferrari R, Camici PG, Crea F et al. Expert consensus document: a “diamond” approach to personalized treatment of angina. Nat Rev Cardiol 2018; 15 (2): 120–32.
3. Ferrari R, Pavasini R, Camici PG et al. Anti-anginal drugs–beliefs and evidence: systematic review covering 50 years of medical treatment. Eur Heart J 2019; 40 (2): 190–4. DOI: doi/10.1093/eurheartj/ehy504/5084899
4. Balla С, Pavasini К, Ferrari R. Treatment of Angina: Where Are We? Cardiology 2018; 140: 52–67. DOI: 10.1159/000487936
5. Laskey et al. Discharge Heart Rate and Outcomes in Heart Failure. J Am Heart Assoc 2015; 4: e001626. DOI: 10.1161/JAHA.114.001626
6. Heusch G. Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: benefit from selective bradycardic agents. Br J Pharmacol 2008; 153: 1589–601.
7. Bassenge E, Heusch G. Endothelial and neuro-humoral control of coronary blood flow in health and disease. Rev Physiol Biochem Pharmacol 1990; 116: 77–165.
8. Traupe T, Gloekler S, de Marchi SF et al. Assessment of the human coronary collateral circulation. Circulation 2010; 122: 1210–20.
9. Heusch G, Yoshimoto N. Effects of heart rate and perfusion pressure on segmental coronary resistances and collateral perfusion. Pflügers Arch 1983; 397: 284–9.
10. Heusch G. Myocardial ischemia: Lack of coronary blood flow or myocardial oxygen supply/ demand imbalance? Circ Res 2016; 119: 194–6.
11. Heusch G. The regional myocardial flow-function relationship: a framework for an understanding of acute ischemia, hibernation, stunning and coronary microembolization. Circ Res 2013; 112: 1535–7.
12. Levy BI, Heusch G, Camici PG. The many faces of myocardial ischemia and angina. Cardiovascular Res 2019; 115: 1460–70. DOI: doi/10.1093/cvr/cvz160/5522026
13. Custodis F, Schirmer SH, Baumhäkel M et al. Vascular pathophysiology in response to increased heart rate. J Am Coll Cardiol 2010; 56: 1973–83.
14. Monnet X, Ghaleh B, Colin P et al. Effects of heart rate reduction with ivabradine on exercise induced myocardial ischemia and stunning. J Pharmacol Exp Ther 2001; 299: 1133–9.
15. Heusch G, Skyschally A, Gres P et al. Improvement of regional myocardial blood flow and function and reduction of infarct size with ivabradine: protection beyond heart rate reduction. Eur Heart J 2008; 29: 2265–75.
16. Gloekler S, Traupe T, Stoller M et al. The effect of heart rate reduction by ivabradine on collateral function in patients with chronic stable coronary artery disease. Heart 2014; 100: 160–6.
17. Monnet X, Colin P, Ghaleh B et al. Heart rate reduction during exercise-induced myocardial ischaemia and stunning. Eur Heart J 2004; 25: 579–86.
18. Maranta F, Tondi L, Agricola E et al. Ivabradine reduces myocardial stunning in patients with exercise-inducible ischaemia. Basic Res Cardiol 2015; 110: 55.
19. Kleinbongard P, Gedik N, Witting P et al. Pleiotropic, heart rate-independent cardioprotection by ivabradine. Br J Pharmacol 2015; 172: 43804390.
20. Heusch G, Kleinbongard P. Ivabradine: Cardioprotection By and Beyond Heart Rate Reduction. Drugs 2016; 76: 733–40.
21. Fox K, Ford I, Steg PJ et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomized, double-blind, placebo-controlled trial. Lancet 2008; 372: 807–16.
22. Fox K, Ford I, Steg PJ et al. Relationship between Ivabradine treatment and cardiovascular outcomes in patients with stable coronary artery disease and left-ventricular systolic dysfunction with limiting angina: a subgroup analysis of the randomized, controlled BEAUTIFUL trial. Eur Heart J 2009; 30: 2337–45.
23. Tardif JC, Ponikowski P, Kahan T; ASSOCIATE Study Investigators. Efficacy of the I(f) current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4-month, randomized, placebo-controlled trial. Eur Heart J 2009; 30 (5): 540–8.
24. Tardif JC, Ponikowski P, Kahan T; ASSOCIATE Study Investigators. Effects of ivabradine in patients with stable angina receiving -blockers according to baseline heart rate: an analysis of the ASSOCIATE study. Int J Cardiol 2013; 168 (2): 789–94.
25. Amosova E, Andrejev E, Zaderey I et al. Efficacy of ivabradine in combination with Betablocker versus uptitration of Beta-blocker in patients with stable angina. Cardiovasc Drugs Ther 2011; 25 (6): 531–7.
26. Williams B, Mancia G, Spiering W et al. 2018 ESC/ESH 2013 ESC guidelines for the management of arterial hypertension: the Task Force on the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur Heart J 2018; 00: 1–98. DOI: 10.1093/eurheartj/ehy339
27. Qiu S, Cai X, Sun Z et al. Heart Rate Recovery and Risk of Cardiovascular Events and All-CauseMortality: A Meta-Analysis of Prospective Cohort Studies. J Am Heart Assoc 2017; 6:e005505. DOI: 10.1161/JAHA.117.005505
28. Divchev D, Stöckl G; study investigators. Treatment of Stable Angina with a New FixedDose Combination of Ivabradine and Metoprolol: Effectiveness and Tolerability in Routine Clinical Practice. Cardiol Ther 2017; 6 (2): 239–49.
29. Kaski JC, Crea F, Gersh BJ, Camici PG. Reappraisal of Ischemic Heart Disease: Fundamental Role of Coronary Microvascular Dysfunction in the Pathogenesis of Angina Pectoris. Circulation 2018; 138: 1463–80.
2. Ferrari R, Camici PG, Crea F et al. Expert consensus document: a “diamond” approach to personalized treatment of angina. Nat Rev Cardiol 2018; 15 (2): 120–32.
3. Ferrari R, Pavasini R, Camici PG et al. Anti-anginal drugs–beliefs and evidence: systematic review covering 50 years of medical treatment. Eur Heart J 2019; 40 (2): 190–4. DOI: doi/10.1093/eurheartj/ehy504/5084899
4. Balla С, Pavasini К, Ferrari R. Treatment of Angina: Where Are We? Cardiology 2018; 140: 52–67. DOI: 10.1159/000487936
5. Laskey et al. Discharge Heart Rate and Outcomes in Heart Failure. J Am Heart Assoc 2015; 4: e001626. DOI: 10.1161/JAHA.114.001626
6. Heusch G. Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: benefit from selective bradycardic agents. Br J Pharmacol 2008; 153: 1589–601.
7. Bassenge E, Heusch G. Endothelial and neuro-humoral control of coronary blood flow in health and disease. Rev Physiol Biochem Pharmacol 1990; 116: 77–165.
8. Traupe T, Gloekler S, de Marchi SF et al. Assessment of the human coronary collateral circulation. Circulation 2010; 122: 1210–20.
9. Heusch G, Yoshimoto N. Effects of heart rate and perfusion pressure on segmental coronary resistances and collateral perfusion. Pflügers Arch 1983; 397: 284–9.
10. Heusch G. Myocardial ischemia: Lack of coronary blood flow or myocardial oxygen supply/ demand imbalance? Circ Res 2016; 119: 194–6.
11. Heusch G. The regional myocardial flow-function relationship: a framework for an understanding of acute ischemia, hibernation, stunning and coronary microembolization. Circ Res 2013; 112: 1535–7.
12. Levy BI, Heusch G, Camici PG. The many faces of myocardial ischemia and angina. Cardiovascular Res 2019; 115: 1460–70. DOI: doi/10.1093/cvr/cvz160/5522026
13. Custodis F, Schirmer SH, Baumhäkel M et al. Vascular pathophysiology in response to increased heart rate. J Am Coll Cardiol 2010; 56: 1973–83.
14. Monnet X, Ghaleh B, Colin P et al. Effects of heart rate reduction with ivabradine on exercise induced myocardial ischemia and stunning. J Pharmacol Exp Ther 2001; 299: 1133–9.
15. Heusch G, Skyschally A, Gres P et al. Improvement of regional myocardial blood flow and function and reduction of infarct size with ivabradine: protection beyond heart rate reduction. Eur Heart J 2008; 29: 2265–75.
16. Gloekler S, Traupe T, Stoller M et al. The effect of heart rate reduction by ivabradine on collateral function in patients with chronic stable coronary artery disease. Heart 2014; 100: 160–6.
17. Monnet X, Colin P, Ghaleh B et al. Heart rate reduction during exercise-induced myocardial ischaemia and stunning. Eur Heart J 2004; 25: 579–86.
18. Maranta F, Tondi L, Agricola E et al. Ivabradine reduces myocardial stunning in patients with exercise-inducible ischaemia. Basic Res Cardiol 2015; 110: 55.
19. Kleinbongard P, Gedik N, Witting P et al. Pleiotropic, heart rate-independent cardioprotection by ivabradine. Br J Pharmacol 2015; 172: 43804390.
20. Heusch G, Kleinbongard P. Ivabradine: Cardioprotection By and Beyond Heart Rate Reduction. Drugs 2016; 76: 733–40.
21. Fox K, Ford I, Steg PJ et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomized, double-blind, placebo-controlled trial. Lancet 2008; 372: 807–16.
22. Fox K, Ford I, Steg PJ et al. Relationship between Ivabradine treatment and cardiovascular outcomes in patients with stable coronary artery disease and left-ventricular systolic dysfunction with limiting angina: a subgroup analysis of the randomized, controlled BEAUTIFUL trial. Eur Heart J 2009; 30: 2337–45.
23. Tardif JC, Ponikowski P, Kahan T; ASSOCIATE Study Investigators. Efficacy of the I(f) current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4-month, randomized, placebo-controlled trial. Eur Heart J 2009; 30 (5): 540–8.
24. Tardif JC, Ponikowski P, Kahan T; ASSOCIATE Study Investigators. Effects of ivabradine in patients with stable angina receiving -blockers according to baseline heart rate: an analysis of the ASSOCIATE study. Int J Cardiol 2013; 168 (2): 789–94.
25. Amosova E, Andrejev E, Zaderey I et al. Efficacy of ivabradine in combination with Betablocker versus uptitration of Beta-blocker in patients with stable angina. Cardiovasc Drugs Ther 2011; 25 (6): 531–7.
26. Williams B, Mancia G, Spiering W et al. 2018 ESC/ESH 2013 ESC guidelines for the management of arterial hypertension: the Task Force on the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur Heart J 2018; 00: 1–98. DOI: 10.1093/eurheartj/ehy339
27. Qiu S, Cai X, Sun Z et al. Heart Rate Recovery and Risk of Cardiovascular Events and All-CauseMortality: A Meta-Analysis of Prospective Cohort Studies. J Am Heart Assoc 2017; 6:e005505. DOI: 10.1161/JAHA.117.005505
28. Divchev D, Stöckl G; study investigators. Treatment of Stable Angina with a New FixedDose Combination of Ivabradine and Metoprolol: Effectiveness and Tolerability in Routine Clinical Practice. Cardiol Ther 2017; 6 (2): 239–49.
29. Kaski JC, Crea F, Gersh BJ, Camici PG. Reappraisal of Ischemic Heart Disease: Fundamental Role of Coronary Microvascular Dysfunction in the Pathogenesis of Angina Pectoris. Circulation 2018; 138: 1463–80.
Авторы
Т.В. Адашева*1, Е.И. Саморукова1, Л.Б. Ахмедярова2, Д.В. Одинцова2
1 ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Минздрава России, Москва, Россия;
2 Больница Центросоюза Российской Федерации, Москва, Россия
*adashtv@mail.ru
1 ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Минздрава России, Москва, Россия;
2 Больница Центросоюза Российской Федерации, Москва, Россия
*adashtv@mail.ru
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Tatiana V. Adasheva*1, Elena I. Samorukova1, Leili B. Akhmedyarova2, Dina V. Odintsova2
1 Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia;
2 Centrosoyuz Hospital, Moscow, Russia
*adashtv@mail.ru
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