medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2023-456medsovet-7989Research ArticleКАРДИОЛОГИЯCARDIOLOGYСовременные представления о роли ранолазина в лечении пациентов со стенокардиейCurrent ideas about the role of ranolazine in patients’ treatment with angina pectorishttps://orcid.org/0000-0002-8505-1848ГиляревскийС. Р.GilyarevskiyS. R.

Гиляревский Сергей Руджерович -д.м.н., профессор, ведущий научный сотрудник лаборатории сердечно-сосудистого старения, РНИМУ имени Н.И. Пирогова, профессор кафедры клинической фармакологии и терапии имени академика Б.Е. Вотчала РМАНПО; Researcher ID: AAN-4179-2021.

129226, Москва, ул. 1-я Леонова, д. 16; 125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Sergey R. Gilyarevskiy -Dr. Sci. (Med.), Professor, Leading Researcher, Laboratory of Cardiovascular Aging, Pirogov RNRMU; Professor, Department of Clinical Pharmacology and Therapy named after Acad. B.E. Votchal, RMA CPER, ID: AAN-4179-2021.

16, 1st Leonov St., Moscow, 129226; 2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

sgilarevsky@rambler.ruhttps://orcid.org/0000-0002-4193-688XТкачеваО. Н.TkachevaO. N.

Ткачева Ольга Николаевна -чл.-корр. РАН, д.м.н., профессор, директор РГНКЦ; РНИМУ имени Н.И. Пирогова; главный внештатный гериатр Министерства здравоохранения Российской Федерации.

129226, Москва, ул. 1-я Леонова, д. 16

Olga N. Tkacheva -Corr. Member RAS, Dr. Sci. (Med.), Professor, Director, Russian Gerontological Research and Clinical Center; Pirogov RNRMU, Chief Freelance Geriatrician of the Ministry of Health of the Russian Federation.

16, 1st Leonov St., Moscow, 129226

Tkacheva@rambler.ruРоссийский национальный исследовательский медицинский университет имени Н.И. Пирогова; Российская медицинская академия непрерывного профессионального образованияРоссияPirogov Russian National Research Medical University; Russian Medical Academy of Continuous Professional EducationRussian FederationРоссийский национальный исследовательский медицинский университет имени Н.И. ПироговаРоссияPirogov Russian National Research Medical UniversityRussian Federation2023180120240232631Copyright © Гиляревский С.Р., Ткачева О.Н., 20242024Гиляревский С.Р., Ткачева О.Н.Gilyarevskiy S.R., Tkacheva O.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/7989

Статья посвящена современным представлениям о роли противоишемического препарата ранолазина в лечении широкого круга пациентов со стенокардией. Приводятся данные об увеличении доли пациентов с хроническим течением коронарной болезни сердца, которым необходимо усовершенствование противоишемической терапии. Необходимость использования альтернативных средств для лечения стенокардии, которая отмечена в статье, определяется увеличением доли пациентов со стенокардией пожилого и старческого возраста, так как у таких пациентов нередко бывают сопутствующие заболевания, ограничивающие использование противоишемических препаратов с гемодинамическим действием. Рассматриваются различные патофизиологические звенья развития ишемии миокарда, которые могут становиться основанием для выбора определенного противоишемического препарата. В частности, приводятся данные о доказанной эффективности применения ранолазина у пациентов со стенокардией и ишемией миокарда, но в отсутствие обструкции коронарных артерий. Подробно обсуждаются механизмы действия ранолазина, которые определяют как его противоишемический, так и плейотропные эффекты. Отмечаются особые эффекты ранолазина, которые могут быть полезны для пациентов с коронарной болезнью сердца и клинически значимым нарушением диастолической функции. Такой эффект состоял в положительном влиянии приема ранолазина на диастолическую функцию левого желудочка. Приводятся данные об экономической эффективности использования ранолазина при лечении стенокардии. Отдельно рассматривается антиаритмическое действие ранолазина. В статье обсуждается переносимость приема ранолазина и возможные побочные эффекты. Подчеркивается в целом хорошая переносимость и высокая безопасность приема ранолазина у широкого круга пациентов с коронарной болезнью сердца.

The article presents modern views on the role of the anti-ischemic agent, ranolazine, in the treatment of a wide range of patients with angina pectoris. It also provides data on a percentage increase in the number of patients with chronic coronary artery disease who need improved anti-ischemic therapy. The need to use alternative agents for the treatment of angina, which is highlighted in the article, is determined by a percentage increase in the number of elderly and senile patients with angina, as such patients often have concomitant diseases that limit the use of haemodynamic anti-ischemic agents. The authors consider various pathophysiological links in the development of myocardial ischemia, which may become the background for choosing a specific anti-ischemic agent. Amongst others, the article provides evidence data on the effectiveness of the usage of ranolazine in patients with angina pectoris and myocardial ischemia, but in the absence of coronary artery obstruction. The mechanisms of action of ranolazine, which determine both its anti-ischemic and pleiotropic effects, are discussed in detail. Special effects of ranolazine that may be beneficial for patients with coronary artery disease and clinically significant diastolic dysfunction are observed. This effect consisted of a positive effect of ranolazine on the left ventricular diastolic function. Data on the cost-effectiveness of the usage of ranolazine in the treatment of angina pectoris are provided. The antiarrhythmic action of ranolazine is considered separately. The article discusses the tolerability of ranolazine and its possible side effects. The all-round good tolerability and high safety of ranolazine in a wide range of patients with coronary artery disease are emphasized.

ишемическая болезнь сердцастенокардияпротивоишемические препаратыранолазинантиаритмический эффектдиастолическая функция сердцаcoronary artery diseaseangina pectorisanti-ischemic drugsranolazineanti-arrhythmic effectdiastolic heart functionReferencesBoden WE, Marzilli M, Crea F, Mancini GBJ, Weintraub WS, Taqueti VR et al. Evolving Management Paradigm for Stable Ischemic Heart Disease Patients: JACC Review Topic of the Week. J Am Coll Cardiol. 2023;81(5):505–514. https://doi.org/10.1016/j.jacc.2022.08.814.Boden WE, Marzilli M, Crea F, Mancini GBJ, Weintraub WS, Taqueti VR et al. Evolving Management Paradigm for Stable Ischemic Heart Disease Patients: JACC Review Topic of the Week. J Am Coll Cardiol. 2023;81(5):505–514. https://doi.org/10.1016/j.jacc.2022.08.814.Hochman JS, Anthopolos R, Reynolds HR, Bangalore S, Xu Y, O’Brien SM et al. Survival After Invasive or Conservative Management of Stable Coronary Disease. Circulation. 2023;147(1):8–19. https://doi.org/10.1161/CIRCULATIONAHA.122.062714.Hochman JS, Anthopolos R, Reynolds HR, Bangalore S, Xu Y, O’Brien SM et al. Survival After Invasive or Conservative Management of Stable Coronary Disease. Circulation. 2023;147(1):8–19. https://doi.org/10.1161/CIRCULATIONAHA.122.062714.Kaski JC, Crea F, Gersh BJ, Camici PG. Reappraisal of Ischemic Heart Disease. Circulation. 2018;138(14):1463–1480. https://doi.org/10.1161/CIRCULATIONAHA.118.031373.Kaski JC, Crea F, Gersh BJ, Camici PG. Reappraisal of Ischemic Heart Disease. Circulation. 2018;138(14):1463–1480. https://doi.org/10.1161/CIRCULATIONAHA.118.031373.SCOT-HEART investigators. CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial. Lancet. 2015;385(9985):2383–2391. https://doi.org/10.1016/S0140-6736(15)60291-4.SCOT-HEART investigators. CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial. Lancet. 2015;385(9985):2383–2391. https://doi.org/10.1016/S0140-6736(15)60291-4.Nanna MG, Wang SY, Damluji AA. Management of Stable Angina in the Older Adult Population. Circ Cardiovasc Interv. 2023;16(4):e012438. https://doi.org/10.1161/CIRCINTERVENTIONS.122.012438.Nanna MG, Wang SY, Damluji AA. Management of Stable Angina in the Older Adult Population. Circ Cardiovasc Interv. 2023;16(4):e012438. https://doi.org/10.1161/CIRCINTERVENTIONS.122.012438.Zaza A, Belardinelli L, Shryock JC. Pathophysiology and pharmacology of the cardiac “late sodium current”. Pharmacol Ther. 2008;119(3):326–339. https://doi.org/10.1016/j.pharmthera.2008.06.001.Zaza A, Belardinelli L, Shryock JC. Pathophysiology and pharmacology of the cardiac “late sodium current”. Pharmacol Ther. 2008;119(3):326–339. https://doi.org/10.1016/j.pharmthera.2008.06.001.Saint DA. The cardiac persistent sodium current: an appealing therapeutic target? Br J Pharmacol. 2008;153(6):1133–1142. https://doi.org/10.1038/sj.bjp.0707492.Saint DA. The cardiac persistent sodium current: an appealing therapeutic target? Br J Pharmacol. 2008;153(6):1133–1142. https://doi.org/10.1038/sj.bjp.0707492.Shryock JC, Belardinelli L. Inhibition of late sodium current to reduce electrical and mechanical dysfunction of ischaemic myocardium. Br J Pharmacol. 2008;153(6):1128–1132. https://doi.org/10.1038/sj.bjp.0707522.Shryock JC, Belardinelli L. Inhibition of late sodium current to reduce electrical and mechanical dysfunction of ischaemic myocardium. Br J Pharmacol. 2008;153(6):1128–1132. https://doi.org/10.1038/sj.bjp.0707522.Ambrosio G, Mugelli A, Lopez-Sendón J, Tamargo J, Camm J. Management of stable angina: A commentary on the European Society of Cardiology guidelines. Eur J Prev Cardiol. 2016;23(13):1401–1412. https://doi.org/10.1177/2047487316648475.Ambrosio G, Mugelli A, Lopez-Sendón J, Tamargo J, Camm J. Management of stable angina: A commentary on the European Society of Cardiology guidelines. Eur J Prev Cardiol. 2016;23(13):1401–1412. https://doi.org/10.1177/2047487316648475.Manolis AJ, Poulimenos LE, Ambrosio G, Kallistratos MS, Lopez-Sendon J, Dechend R et al. Medical treatment of stable angina: A tailored therapeutic approach. Int J Cardiol. 2016;220:445–453. https://doi.org/10.1016/j.ijcard.2016.06.150.Manolis AJ, Poulimenos LE, Ambrosio G, Kallistratos MS, Lopez-Sendon J, Dechend R et al. Medical treatment of stable angina: A tailored therapeutic approach. Int J Cardiol. 2016;220:445–453. https://doi.org/10.1016/j.ijcard.2016.06.150.Hasenfuss G, Maier LS. Mechanism of action of the new anti-ischemia drug ranolazine. Clin Res Cardiol. 2008;97(4):222–226. https://doi.org/10.1007/s00392-007-0612-y.Hasenfuss G, Maier LS. Mechanism of action of the new anti-ischemia drug ranolazine. Clin Res Cardiol. 2008;97(4):222–226. https://doi.org/10.1007/s00392-007-0612-y.Tamargo J, Lopez-Sendon J. Ranolazine: a better understanding of its pathophysiology and patient profile to guide treatment of chronic stable angina. Future Cardiol. 2022;18(3):235–251. https://doi.org/10.2217/fca2021-0058.Tamargo J, Lopez-Sendon J. Ranolazine: a better understanding of its pathophysiology and patient profile to guide treatment of chronic stable angina. Future Cardiol. 2022;18(3):235–251. https://doi.org/10.2217/fca2021-0058.Wernhart S, Papathanasiou M, Rassaf T, Luedike P. The controversial role of beta-blockers in heart failure with preserved ejection fraction. Pharmacol Ther. 2023;243:108356. https://doi.org/10.1016/j.pharmthera.2023.108356.Wernhart S, Papathanasiou M, Rassaf T, Luedike P. The controversial role of beta-blockers in heart failure with preserved ejection fraction. Pharmacol Ther. 2023;243:108356. https://doi.org/10.1016/j.pharmthera.2023.108356.Komajda M, Isnard R, Cohen-Solal A, Metra M, Pieske B, Ponikowski P et al. Effect of ivabradine in patients with heart failure with preserved ejection fraction: the EDIFY randomized placebo-controlled trial. Eur J Heart Fail. 2017;19(11):1495–1503. https://doi.org/10.1002/ejhf.876.Komajda M, Isnard R, Cohen-Solal A, Metra M, Pieske B, Ponikowski P et al. Effect of ivabradine in patients with heart failure with preserved ejection fraction: the EDIFY randomized placebo-controlled trial. Eur J Heart Fail. 2017;19(11):1495–1503. https://doi.org/10.1002/ejhf.876.Cempaka Putri DKS, Andrianto A, Al-Farabi MJ, Saputra PBT, Nugraha RA. Efficacy of Ranolazine to Improve Diastolic Performance in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-analysis. Eur Cardiol. 2023;18:e02. https://doi.org/10.15420/ecr.2022.10.Cempaka Putri DKS, Andrianto A, Al-Farabi MJ, Saputra PBT, Nugraha RA. Efficacy of Ranolazine to Improve Diastolic Performance in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-analysis. Eur Cardiol. 2023;18:e02. https://doi.org/10.15420/ecr.2022.10.Chaitman BR, Skettino SL, Parker JO, Hanley P, Meluzin J, Kuch J et al. Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol. 2004;43(8):1375–1382. https://doi.org/10.1016/j.jacc.2003.11.045.Chaitman BR, Skettino SL, Parker JO, Hanley P, Meluzin J, Kuch J et al. Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol. 2004;43(8):1375–1382. https://doi.org/10.1016/j.jacc.2003.11.045.Chaitman BR, Pepine CJ, Parker JO, Skopal J, Chumakova G, Kuch J et al. Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial. JAMA. 2004;291(3):309–316. https://doi.org/10.1001/jama.291.3.309.Chaitman BR, Pepine CJ, Parker JO, Skopal J, Chumakova G, Kuch J et al. Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial. JAMA. 2004;291(3):309–316. https://doi.org/10.1001/jama.291.3.309.Stone PH, Gratsiansky NA, Blokhin A, Huang IZ, Meng L. Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol. 2006;48(3):566–575. https://doi.org/10.1016/j.jacc.2006.05.044.Stone PH, Gratsiansky NA, Blokhin A, Huang IZ, Meng L. Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol. 2006;48(3):566–575. https://doi.org/10.1016/j.jacc.2006.05.044.Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Murphy SA, Budaj A, Varshavsky S et al. Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. JAMA. 2007;297(16):1775–1783. https://doi.org/10.1001/jama.297.16.1775.Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Murphy SA, Budaj A, Varshavsky S et al. Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. JAMA. 2007;297(16):1775–1783. https://doi.org/10.1001/jama.297.16.1775.Wilson SR, Scirica BM, Braunwald E, Murphy SA, Karwatowska-Prokopczuk E, Buros JL et al. Efficacy of ranolazine in patients with chronic angina observations from the randomized, double-blind, placebo-controlled MERLIN-TIMI (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Segment Elevation Acute Coronary Syndromes) 36 Trial. J Am Coll Cardiol. 2009;53(17):1510–1516. https://doi.org/10.1016/j.jacc.2009.01.037.Wilson SR, Scirica BM, Braunwald E, Murphy SA, Karwatowska-Prokopczuk E, Buros JL et al. Efficacy of ranolazine in patients with chronic angina observations from the randomized, double-blind, placebo-controlled MERLIN-TIMI (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Segment Elevation Acute Coronary Syndromes) 36 Trial. J Am Coll Cardiol. 2009;53(17):1510–1516. https://doi.org/10.1016/j.jacc.2009.01.037.Gutierrez JA, Karwatowska-Prokopczuk E, Murphy SA, Belardinelli L, Farzaneh-Far R, Walker G et al. Effects of Ranolazine in Patients With Chronic Angina in Patients With and Without Percutaneous Coronary Intervention for Acute Coronary Syndrome: Observations From the MERLIN-TIMI 36 Trial. Clin Cardiol. 2015;38(8):469–475. https://doi.org/10.1002/clc.22425.Gutierrez JA, Karwatowska-Prokopczuk E, Murphy SA, Belardinelli L, Farzaneh-Far R, Walker G et al. Effects of Ranolazine in Patients With Chronic Angina in Patients With and Without Percutaneous Coronary Intervention for Acute Coronary Syndrome: Observations From the MERLIN-TIMI 36 Trial. Clin Cardiol. 2015;38(8):469–475. https://doi.org/10.1002/clc.22425.Bennett NM, Iyer V, Arndt TL, Garberich RF, Traverse JH, Johnson RK et al. Ranolazine refractory angina registry: 1-year results. Crit Pathw Cardiol. 2014;13(3):96–98. https://doi.org/10.1097/HPC.0000000000000022.Bennett NM, Iyer V, Arndt TL, Garberich RF, Traverse JH, Johnson RK et al. Ranolazine refractory angina registry: 1-year results. Crit Pathw Cardiol. 2014;13(3):96–98. https://doi.org/10.1097/HPC.0000000000000022.Venkataraman R, Belardinelli L, Blackburn B, Heo J, Iskandrian AE. A study of the effects of ranolazine using automated quantitative analysis of serial myocardial perfusion images. JACC Cardiovasc Imaging. 2009;2(11):1301–1309. https://doi.org/10.1016/j.jcmg.2009.09.006.Venkataraman R, Belardinelli L, Blackburn B, Heo J, Iskandrian AE. A study of the effects of ranolazine using automated quantitative analysis of serial myocardial perfusion images. JACC Cardiovasc Imaging. 2009;2(11):1301–1309. https://doi.org/10.1016/j.jcmg.2009.09.006.Tagliamonte E, Rigo F, Cirillo T, Astarita C, Quaranta G, Marinelli U et al. Effects of ranolazine on noninvasive coronary flow reserve in patients with myocardial ischemia but without obstructive coronary artery disease. Echocardiography. 2015;32(3):516–521. https://doi.org/10.1111/echo.12674.Tagliamonte E, Rigo F, Cirillo T, Astarita C, Quaranta G, Marinelli U et al. Effects of ranolazine on noninvasive coronary flow reserve in patients with myocardial ischemia but without obstructive coronary artery disease. Echocardiography. 2015;32(3):516–521. https://doi.org/10.1111/echo.12674.Mehta PK, Goykhman P, Thomson LE, Shufelt C, Wei J, Yang Y et al. Ranolazine improves angina in women with evidence of myocardial ischemia but no obstructive coronary artery disease. JACC Cardiovasc Imaging. 2011;4(5):514–522. https://doi.org/10.1016/j.jcmg.2011.03.007.Mehta PK, Goykhman P, Thomson LE, Shufelt C, Wei J, Yang Y et al. Ranolazine improves angina in women with evidence of myocardial ischemia but no obstructive coronary artery disease. JACC Cardiovasc Imaging. 2011;4(5):514–522. https://doi.org/10.1016/j.jcmg.2011.03.007.Timmis AD, Chaitman BR, Crager M. Effects of ranolazine on exercise tolerance and HbA1c in patients with chronic angina and diabetes. Eur Heart J. 2006;27(1):42–48. https://doi.org/10.1093/eurheartj/ehi495.Timmis AD, Chaitman BR, Crager M. Effects of ranolazine on exercise tolerance and HbA1c in patients with chronic angina and diabetes. Eur Heart J. 2006;27(1):42–48. https://doi.org/10.1093/eurheartj/ehi495.Ayyasamy L, Bagepally BS. Cost-utility of Ranolazine for Chronic Stable Angina Pectoris: Systematic Review and Meta-analysis. Clin Ther. 2023;45(5):458–465. https://doi.org/10.1016/j.clinthera.2023.04.004.Ayyasamy L, Bagepally BS. Cost-utility of Ranolazine for Chronic Stable Angina Pectoris: Systematic Review and Meta-analysis. Clin Ther. 2023;45(5):458–465. https://doi.org/10.1016/j.clinthera.2023.04.004.Hasenfuss G, Maier LS. Mechanism of action of the new anti-ischemia drug ranolazine. Clin Res Cardiol. 2008;97(4):222–226. https://doi.org/10.1007/s00392-007-0612-y.Hasenfuss G, Maier LS. Mechanism of action of the new anti-ischemia drug ranolazine. Clin Res Cardiol. 2008;97(4):222–226. https://doi.org/10.1007/s00392-007-0612-y.Scirica BM, Morrow DA. Ranolazine in patients with angina and coronary artery disease. Curr Cardiol Rep. 2007;9(4):272–278. https://doi.org/10.1007/BF02938375.Scirica BM, Morrow DA. Ranolazine in patients with angina and coronary artery disease. Curr Cardiol Rep. 2007;9(4):272–278. https://doi.org/10.1007/BF02938375.Scirica BM, Morrow DA, Hod H, Murphy SA, Belardinelli L, Hedgepeth CM et al. Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of arrhythmias in patients with non ST-segment elevation acute coronary syndrome: results from the Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation. 2007;116(15):1647–16452. https://doi.org/10.1161/CIRCULATIONAHA.107.724880.Scirica BM, Morrow DA, Hod H, Murphy SA, Belardinelli L, Hedgepeth CM et al. Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of arrhythmias in patients with non ST-segment elevation acute coronary syndrome: results from the Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation. 2007;116(15):1647–16452. https://doi.org/10.1161/CIRCULATIONAHA.107.724880.Koren MJ, Crager MR, Sweeney M. Long-term safety of a novel antianginal agent in patients with severe chronic stable angina: the Ranolazine Open Label Experience (ROLE). J Am Coll Cardiol. 2007;49(10):1027–1034. https://doi.org/10.1016/j.jacc.2006.10.067.Koren MJ, Crager MR, Sweeney M. Long-term safety of a novel antianginal agent in patients with severe chronic stable angina: the Ranolazine Open Label Experience (ROLE). J Am Coll Cardiol. 2007;49(10):1027–1034. https://doi.org/10.1016/j.jacc.2006.10.067.

The authors declare that there are no conflicts of interest present.