New perspectives and real possibilities in the treatment of patients with heart failure


DOI: https://dx.doi.org/10.18565/therapy.2021.6.91-97

Shulkina S.G., Kokorin V.A.

1) Perm State Medical University named after Academician E.A. Vagner of the Ministry of Healthcare of Russia; 2) N.I. Pirogov Russian National Research Medical University of the Ministry of Healthcare of Russia, Moscow
Abstract. Effective treatment of chronic heart failure (CHF), with a focus on reducing mortality and improving the quality of life of patients is an urgent public health problem. Sodium-glucose cotransporter-2 inhibitors are currently one of the most interesting and studied classes of drugs that demonstrate an improved prognosis in patients with cardiovascular diseases in diabetic and nondiabetic populations. The article describes in detail the known mechanisms of cardioprotective and nephroprotective effects of this class of drugs. A detailed review of studies published in recent years on the study of dapagliflozin on cardiovascular and renal outcomes in patients with diabetes mellitus is presented. Particular attention is paid to the analysis of the DAPA-HF study, which proved the effectiveness of using dapagliflozin in addition to standard therapy in patients with CHF with reduced ejection fraction.
Keywords: cardioprotective and nephroprotective effects, sodium-glucose cotransporter-2 inhibitors, dapagliflozin, heart failure
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Literature


  1. Указ Президента РФ от 07.05.2018 № 204 «О национальных целях и стратегических задачах развития Российской Федерации на период до 2024 года». Доступ: https://www.garant.ru/products/ipo/prime/doc/71837200 (дата обращения – 10.03.2021). [Decree of the President of the Russian Federation No. 204 of May 7, 2018 «On National goals and strategic objectives for the development of the Russian Federation for the period up to 2024». Available at: https://www.garant.ru/products/ipo/prime/doc/71837200 (date of access – 10.03.2021) (In Russ.)].

  2. Журавлева М.В., Терещенко С.Н., Жиров И.В. с соавт. Оценка влияния применения лекарственного препарата дапаглифлозин у пациентов с хронической сердечной недостаточностью на достижение целевого показателя федерального проекта «Борьба с сердечно-сосудистыми заболеваниями» – снижение смертности от болезней системы кровообращения. Российский кардиологический журнал. 2020; 10: 94–103. [Zhuravleva M. V., Tereshchenko S. N., Zhirov I. V. et al. Effect of dapagliflozin in patients with heart failure on reducing cardiovascular mortality in federal project on the prevention of cardiovascular diseases. Rossiyskiy kardiologicheskiy zhurnal = Russian journal of cardiology. 2020; 10: 94–103 (In Russ.)]. doi: https://dx.doi.org/10.15829/1560-4071-2020-4142.

  3. Savarese G., Lund L.H. Global public health burden of heart failure. Card Fail Rev. 2017; 3(1): 7–11. doi: 10.15420/cfr.2016:25:2.

  4. Шляхто Е.В., Звартау Н.Э., Виллевальде С.В. с соавт. Значимость оценки распространенности и мониторинга исходов у пациентов с сердечной недостаточностью в России. Российский кардиологический журнал. 2020; 12: 146–154. [Shlyakhto E.V., Zvartau N.E., Villevalde S.V. et al. Assessment of prevalence and monitoring of outcomes in patients with heart failure in Russia. Rossiyskiy kardiologicheskiy zhurnal = Russian journal of cardiology. 2020; 12: 146–154 (In Russ.)]. doi: https://dx.doi.org/10.15829/1560-4071-2020-4204.

  5. Хроническая сердечная недостаточность. Клинические рекомендации 2020. Российский кардиологический журнал. 2020; 11: 311–374. [2020 Clinical practice guidelines for chronic heart failure. Rossiyskiy kardiologicheskiy zhurnal = Russian journal of cardiology. 2020; 11: 311–374 (In Russ.)]. doi: https://dx.doi.org/10.15829/1560-4071-2020-4083.

  6. Abajobir A.A., Abate K.H., Abbafati C. et al. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018; 392(10159): 1789–858. doi: 10.1016/S0140-6736(18)32279-7.

  7. Фомин И.В. Хроническая сердечная недостаточность в Российской Федерации: что сегодня мы знаем и что должны делать. Российский кардиологический журнал. 2016; 8: 7–13. [Fomin I.V. Chronic heart failure in Russian Federation: what do we know and what to do. Rossiyskiy kardiologicheskiy zhurnal = Russian journal of cardiology. 2016; 8: 7–13 (In Russ.)]. doi: https://dx.doi.org/10.15829/1560-4071-2016-8-7-13.

  8. Кобалава Ж.Д., Конради А.О., Недогода С.В. с соавт. Артериальная гипертензия у взрослых. Клинические рекомендации 2020. Российский кардиологический журнал. 2020; 3: 149–218. [Kobalava Zh.D., Konradi A.O., Nedogoda S.V. et al. Arterial hypertension in adults. Clinical guidelines 2020. Rossiyskiy kardiologicheskiy zhurnal = Russian journal of cardiology. 2020; 3: 149–218 (In Russ.) doi: https://dx.doi.org/10.15829/1560-4071-2020-3-3786.

  9. Шестакова М.В., Викулова О.К., Железнякова А.В. с соавт. Эпидемиология сахарного диабета в Российской Федерации: что изменилось за последнее десятилетие? Терапевтический архив. 2019; 10: 4–13. [Shestakova M.V., Vikulova O.K., Zheleznyakova A.V. et al. Diabetes epidemiology in Russia: what has changed over the decade? Therapevticheskiy arkhiv = Therapeutic archive. 2019; 10: 4–13 (In Russ.)]. doi: https://dx.doi.org/10.26442/00403660.2019.10.000364.

  10. Дедов И.И., Шестакова М.В., Майорова А.Ю. с соавт. Алгоритмы специализированной медицинской помощи больным сахарным диабетом / под ред. И.И. Дедова, М.В. Шестаковой, А.Ю. Майорова. 9-й выпуск. Сахарный диабет. 2019; S1–1: 1–144. [Dedov I.I., Shestakova M.V., Mayorov A.Yu. et al. Standards of specialized diabetes care. Edited by Dedov I.I., Shestakova M.V., Mayorov A.Yu. 9th edition. Sakharny diabet = Diabetes mellitus. 2019; S1–1: 1–144 (In Russ.)]. doi: https://dx.doi.org/10.14341/DM221S1.

  11. Бойцов С.А., Голухова Е.З., Драпкина О.М. с соавт. Смертность населения от различных болезней системы кровообращения в Москве и Санкт-Петербурге в 2015 и 2018 годах. Российский кардиологический журнал. 2021; 1: 73–78. [Boytsov S.A., Golukhova E.Z., Drapkina O.M. et al. Cardiovascular mortality rate in Moscow and St. Petersburg in 2015 and 2018. Rossiyskiy kardiologicheskiy zhurnal = Russian journal of cardiology. 2021; 1: 73–78 (In Russ.)]. doi: https://dx.doi.org/10.15829/1560-4071-2021-4048.

  12. Шляхто Е.В., Баранова Е.И. Основные направления снижения сердечно-сосудистой смертности: что можно изменить уже сегодня? Российский кардиологический журнал. 2020; 7: 10–18. [Shlyakhto E.V., Baranova E.I. Central directions for reducing cardiovascular mortality: what can be changed today? Rossiyskiy kardiologicheskiy zhurnal = Russian journal of cardiology. 2020; 7: 10–18 (In Russ.)]. doi: https://dx.doi.org/10.15829/1560-4071-2020-3983.

  13. Jones N.R., Roalfe A.K., Adoki I. et al. Survival of patients with chronic heart failure in the community: a systematic review and meta-analysis. Eur J Heart Fai. 2019; 21(11): 1306–25. doi: 10.1002/ejhf.1594.

  14. Rosano G.M., Vitale C., Seferovic P. Heart failure in patients with diabetes mellitus. Card Fail Rev. 2017; 3(1): 52–55. doi: 10.15420/cfr.2016:20:2.

  15. Терещенко С.Н., Шестакова М.В., Агеев Ф.Т. с соавт. Целесообразность назначения дапаглифлозина для профилактики неблагоприятных исходов хронической сердечной недостаточности у пациентов со сниженной фракцией выброса. Резолюция совета экспертов. Российский кардиологический журнал. 2020; 5: 114–120. [Tereshchenko S.N., Shestakova M.V., Ageev F.T. et al. Rationale for dapagliflozin administration for the prevention of adverse outcomes in patients with heart failure with reduced ejection fraction. Expert consensus statement. Rossiyskiy kardiologicheskiy zhurnal = Russian journal of cardiology. 2020; 5: 114–120 (In Russ.)]. doi: https://dx.doi.org/10.15829/1560-4071-2020-3919.

  16. Kluger A.Y., Tecson K.M., Barbin C.M. et al. Cardiorenal outcomes in the CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME trials: a systematic review. Rev Cardiovasc Med. 2018; 19(2): 41–49. doi: 10.31083/j.rcm.2018.02.907.

  17. Zelniker T.A., Wiviott S.D., Raz I. et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019; 393(10166): 31–39. doi: 10.1016/S0140-6736(18)32590-X.

  18. Packer M. SGLT2 inhibitors produce cardiorenal benefits by promoting adaptive cellular reprogramming to induce a state of fasting mimicry: a paradigm shift in understanding their mechanism of action. Diabetes Care. 2020; 43(3): 508–11. doi: 10.2337/dci19-0074.

  19. Инструкция по медицинскому применению лекарственного препарата Форсига с учетом изменений 1–4. РУ: ЛП 002596 от 23.06.20 г. http://grls.rosminzdrav.ru/ (дата обращения – 15.02.2021). [Instructions for the medical use of Forsiga, taking into account changes 1–4. http://grls.rosminzdrav.ru/ (date of access – 15.02.2021) (In Russ.)].

  20. Tahrani A.A., Barnett A.H. Dapagliflozin: a sodium glucose cotransporter 2 inhibitor in development for type 2 diabetes Diabetes Ther. 2010; 1(2): 45–56. doi: 10.1007/s13300-010-0007-3.

  21. Mullens W., Verbrugge F.H., Nijst P., Tang W.H.W. Renal sodium avidity in heart failure: from pathophysiology to treatment strategies. Eur Heart J. 2017; 38(24): 1872–82. doi: 10.1093/eurheartj/ehx035.

  22. Sato T., Aizawa Y., Yuasa S. et al. The effect of dapagliflozin treatment on epicardial adipose tissue volume. Cardiovasc Diabetol. 2018; 17(1): 6. doi: 10.1186/s12933-017-0658-8.

  23. Patoulias D., Papadopoulos C., Stavropoulos K. et al. Prognostic value of arterial stiffness measurements in cardiovascular disease, diabetes, and its complications: The potential role of sodium-glucose co-transporter-2 inhibitors. J Clin Hypertens (Greenwich). 2020; 22(4): 562–71. doi: 10.1111/jch.13831.

  24. Ferrannini E., Mark M., Mayoux E. CV protection in the EMPA-REG OUTCOME trial: a «thrifty substrate» hypothesis. Diabetes Care. 2016; 39(7): 1108–14. doi: 10.2337/dc16-0330.

  25. Mudaliar S., Alloju S., Henry R.R. Can a shift in fuel energetics explain the beneficial cardiorenal outcomes in the EMPA-REG OUTCOME study? A unifying hypothesis. Diabetes Care. 2016; 39(7): 1115–22. doi: 10.2337/dc16-0542.

  26. Uthman L., Baartscheer A., Schumacher C.A. et al. Direct cardiac actions of sodium glucose cotransporter 2 inhibitors target pathogenic mechanisms underlying heart failure in diabetic patients. Front Physiol. 2018; 9: 1575. doi: 10.3389/ fphys.2018.01575.

  27. Uthman, L., Homayr A., Hollmann M.W. et al. Administration of SGLT2 inhibitor empagliflozin against TNF-α induced endothelial dysfunction in human venous and arterial endothelial cells. FASEB J. 2018; 32(S1): 569.4. doi: 10.1096/fasebj.2018.32.1_supplement.569.4.

  28. Tamargo J. Sodium-glucose cotransporter 2 inhibitors in heart failure: Potential mechanisms of action, adverse effects and future developments. Eur Cardiol. 2019; 14(1): 23–32. doi: 10.15420/ecr.2018.34.2.

  29. Rhee J.J., Jardine M.J., Chertow G.M. et al. Dedicated kidney disease-focused outcome trials with sodium-glucose cotransporter-2 inhibitors: lessons from CREDENCE and expectations from DAPA-HF, DAPA-CKD, and EMPA-KIDNEY. Diabetes Obes Metab. 2020; 22(Suppl. 1): 46–54. doi: 10.1111/dom.13987.

  30. Verma S., McMurray J.J.V. SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia. 2018; 61(10): 2108–17. doi: 10.1007/s00125-018-4670-7.

  31. Xin Y., Guo Y., Li Y. et al. Effects of sodium glucose cotransporter-2 inhibitors on serum uric acid in type 2 diabetes mellitus: A systematic review with an indirect comparison meta-analysis. Saudi J Biol Sci. 2019; 26(2): 421–26. doi: 10.1016/j.sjbs.2018.11.013.

  32. Heerspink H.J.L., de Zeeuw D., Wie L. et al. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes Metab. 2013; 15(9): 853–62. doi: 10.1111/dom.12127.

  33. Heerspink H.J.L., Perkins B.A., Fitchett D.H. et al. Sodium glucose сotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation. 2016; 134(10): 752–72. doi: 10.1161/CIRCULATIONAHA.116.021887.

  34. Cosentino F., Grant P.J., Aboyans V. et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020; 41(2): 255–323. doi: 10.1093/eurheartj/ehz486.

  35. Wiviott S.D., Raz I., Bonaca M.P. et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019; 380(4): 347–57. doi: 10.1056/NEJMoa1812389.

  36. Mosenzon O., Wiviott S.D., Cahn A. et al. Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE-TIMI 58 randomised trial. Lancet Diabetes Endocrinol. 2019; 7(8): 606–17. doi: 10.1016/S2213-8587(19)30180-9.

  37. McMurray J.J.V., Solomon S.D., Inzucchi S.E. et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019; 381(21): 1995–2008. doi: 10.1056/NEJMoa1911303.

  38. Docherty K.F., Jhund P.S., Anand I. et al. Effect of dapagliflozin on outpatient worsening of patients with heart failure and reduced ejection fraction: a prespecified analysis of DAPA-HF. Circulation. 2020; 142(17): 1623–32. doi: 10.1161/CIRCULATIONAHA.120.047480.

  39. McMurray J.J.V., De Mets D.L., Inzucchi S.E. et al. The Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial: baseline characteristics. Eur J Heart Fail. 2019; 21(11): 1402–11. doi: 10.1002/ejhf.1548.

  40. KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney International. 2020; 98(4): S1–S115. doi: 10.1016/j.kint.2020.06.019.

  41. Heerspink H.J.L., Stefansson B.V., Correa-Rotter R. et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020; 383(15): 1436–46. doi: 10.1056/NEJMoa2024816.


About the Autors

Sofia G. Shulkina, MD, associate professor of the Department of outpatient therapy, Perm State Medical University named after Academician E.A. Vagner of the Ministry of Healthcare of Russia. Address: 614000, Perm, 26 Petropavlovskaya Str. Tel.: +7 (950) 451-05-26. E-mail: shulkina-s@mail.ru. ORCID: 0000-0002-1686-3885
Valentin A. Kokorin, PhD, associate professor, associate professor of the Department of hospital therapy named after academician P.E. Lukomsky, N.I. Pirogov Russian National Research Medical University of the Ministry of Healthcare of Russia. Address: 117997, Moscow, 1 Ostrovityanova Str. Tel.: +7 (916) 132-96-06. E-mail: valentinkokorin@yahoo.com. ORCID 0000-0001-8614-6542


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