russjcardiolРоссийский кардиологический журналRussian Journal of Cardiology1560-40712618-7620«SILICEA-POLIGRAF» LLC10.15829/1560-4071-2020-3870russjcardiol-3870Research ArticleМНЕНИЕ ПО ПРОБЛЕМЕOPINION ON THE ISSUEНа пути к квадротерапии сердечной недостаточности с низкой фракцией выброса: данные вторичных анализов DAPA-HFTowards quadruple therapy for heart failure with reduced ejection fraction: DAPA-HF secondary analysis datahttps://orcid.org/0000-0003-1126-4282КобалаваЖ. Д.KobalavaZh. D.

Кобалава Жанна Давидовна — член-корреспондент РАН, доктор медицинских наук, профессор, eLibrary SPIN: 9828-5409.

Москва

zkobalava@mail.ruhttps://orcid.org/0000-0001-5996-8305МедовщиковВ. Вл.MedovchshikovV. V.

Медовщиков Вадим Владимирович — аспирант кафедры внутренних болезней с курсом кардиологии и функциональной диагностики им. академика В.С. Моисеева, eLibrary SPIN: 6328-4279.

Москва

vadimedov@gmail.comhttps://orcid.org/0000-0002-5389-754XЕшниязовН. Б.YeshniyazovN. B.

Ешниязов Нурлан Булатович — аспирант кафедры внутренних болезней с курсом кардиологии и функциональной диагностики им. акад. В.С. Моисееева, ORCID: 0000-0002-5389-754X, eLibrary SPIN: 3153-2533.

Москва

eLibrary SPIN: 3153-2533

77017855459@yandex.kzРоссийский университет дружбы народов (РУДН)РоссияPeoples' Friendship University of Russia (RUDN University)Russian Federation20200706202025538703870Copyright © Кобалава Ж.Д., Медовщиков В.В., Ешниязов Н.Б., 20202020Кобалава Ж.Д., Медовщиков В.В., Ешниязов Н.Б.Kobalava Z.D., Medovchshikov V.V., Yeshniyazov N.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://russjcardiol.elpub.ru/jour/article/view/3870

У пациентов с сердечной недостаточностью с низкой фракцией выброса (СН-нФВ), несмотря на наличие доказанных методов лечения, сохраняется высокий остаточный риск неблагоприятных исходов. Положительные результаты исследований по сердечно-сосудистой безопасности и эффективности ингибиторов натрий-глюкозного ко-транспортера 2-го типа (иНГЛТ2) у пациентов с сахарным диабетом 2 типа (СД2), в т.ч. на исходы, связанные с СН, стали основанием для изучения их потенциала у пациентов с СН-нФВ вне зависимости от наличия СД 2 типа. Впервые в исследовании DAPA-HF представитель класса иНГЛТ-2 дапаглифлозин у пациентов с СН-нФВ продемонстрировал положительное влияние на жесткие конечные точки. Данные вторичного анализа подтвердили эффективность дапаглифлозина вне зависимости от статуса СД 2 типа, получаемой медикаментозной терапии, возраста и качества жизни. Результаты DAPA-HF стали серьезной заявкой на изменение стандартов оптимальной медикаментозной терапии СН-нФВ.

Patients with heart failure with reduced ejection fraction (HFrEF), despite optimal evidence-based treatment, have a high residual risk of adverse outcomes. The favorable results of studies on cardiovascular safety and the effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D), including outcomes associated with heart failure, were the reason for studying the effectiveness in patients with HFrEF regardless of the T2D status. For the first time in the DAPA-HF study, the SGLT2 inhibitor dapagliflozin in patients with HFrEF showed a positive effect on hard endpoints. Data of the secondary analysis confirmed the effectiveness of dapagliflozin regardless of the T2D status, therapy, age, and quality of life. The results of DAPA-HF have become a serious statement for changing the standards of the guideline-recommended therapy of HFrEF.

сердечная недостаточностьнизкая фракция выбросасахарный диабет 2 типаингибиторы НГЛТ2дапаглифлозиноптимальная медикаментозная терапияDAPA-HFсубанализheart failurereduced ejection fractiontype 2 diabetesSGLT2 inhibitorsdapagliflozinguideline-recommended therapyDAPA-HFsub-analysisReferencesGregg EW, Li Y, Wang J, et al. Changes in diabetes-related complications in the United States, 1990-2010. N Engl J Med. 2014;370( 16): 1514-23. doi:10.1056/NEJMoa1310799.Gregg EW, Li Y, Wang J, et al. Changes in diabetes-related complications in the United States, 1990-2010. N Engl J Med. 2014;370( 16): 1514-23. doi:10.1056/NEJMoa1310799.Alonso-Moran E, Orueta JF, Fraile Esteban JI, et al. The prevalence of diabetes-related complications and multimorbidity in the population with type 2 diabetes mellitus in the Basque Country. BMC Public Health. 2014;14:1059. doi:10.1186/1471-2458-14-1059.Alonso-Moran E, Orueta JF, Fraile Esteban JI, et al. The prevalence of diabetes-related complications and multimorbidity in the population with type 2 diabetes mellitus in the Basque Country. BMC Public Health. 2014;14:1059. doi:10.1186/1471-2458-14-1059.Shah AD, Langenberg C, Rapsomaniki E, et al. Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1,9 million people. Lancet Diabetes Endocrinol. 2015;3:105-13. doi:10.1016/S2213-8587(14)70219-0.Shah AD, Langenberg C, Rapsomaniki E, et al. Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1,9 million people. Lancet Diabetes Endocrinol. 2015;3:105-13. doi:10.1016/S2213-8587(14)70219-0.Low Wang CC, Hess CN, Hiatt WR, Goldfine AB. Clinical Update: Cardiovascular Disease in Diabetes Mellitus: Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes Mellitus — Mechanisms, Management, and Clinical Considerations. Circulation. 2016;133(24):2459-502. doi:10.1161/circulationaha.116.022194.Low Wang CC, Hess CN, Hiatt WR, Goldfine AB. Clinical Update: Cardiovascular Disease in Diabetes Mellitus: Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes Mellitus — Mechanisms, Management, and Clinical Considerations. Circulation. 2016;133(24):2459-502. doi:10.1161/circulationaha.116.022194.Dei Cas A, Khan SS, Butler J, et al. Impact of Diabetes on Epidemiology, Treatment and Outcomes of Patients with Heart Failure. JACC Heart Failure. 2015;3:136-45. doi:10.1016/j.jchf.2014.08.004.Dei Cas A, Khan SS, Butler J, et al. Impact of Diabetes on Epidemiology, Treatment and Outcomes of Patients with Heart Failure. JACC Heart Failure. 2015;3:136-45. doi:10.1016/j.jchf.2014.08.004.Dauriz M, Mantovani A, Bonapace S, et al. Prognostic Impact of Diabetes on Longterm Survival Outcomes in Patients With Heart Failure: A Meta-analysis. Diabetes Care. 2017;40(11):1597-605. doi:10.2337/dc17-0697.Dauriz M, Mantovani A, Bonapace S, et al. Prognostic Impact of Diabetes on Longterm Survival Outcomes in Patients With Heart Failure: A Meta-analysis. Diabetes Care. 2017;40(11):1597-605. doi:10.2337/dc17-0697.Cavender MA, Steg PG, Smith SC Jr, et al. Impact of diabetes mellitus on hospitalization for heart failure, cardiovascular events, and death: outcomes at 4 years from the Reduction of Atherothrombosis for Continued Health (REACH) Registry. Circulation. 2015;132(10):923-31. doi:10.1161/CIRCULATIONAHA.114.014796.Cavender MA, Steg PG, Smith SC Jr, et al. Impact of diabetes mellitus on hospitalization for heart failure, cardiovascular events, and death: outcomes at 4 years from the Reduction of Atherothrombosis for Continued Health (REACH) Registry. Circulation. 2015;132(10):923-31. doi:10.1161/CIRCULATIONAHA.114.014796.Seferovic PM, Petrie MC, Filippatos GS, et al. Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2018;20(5):853-72. doi:10.1002/ejhf.1170.Seferovic PM, Petrie MC, Filippatos GS, et al. Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2018;20(5):853-72. doi:10.1002/ejhf.1170.Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017;135( 10):e146-e603. doi:10.1161/CIR.0000000000000485.Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017;135( 10):e146-e603. doi:10.1161/CIR.0000000000000485.Lam CSP, Chandramouli C, Ahooja V, Verma S. SGLT-2 Inhibitors in Heart Failure: Current Management, Unmet Needs, and Therapeutic Prospects. J Am Heart Assoc. 2019;8(20):e013389. doi:10.1161/JAHA.119.013389.Lam CSP, Chandramouli C, Ahooja V, Verma S. SGLT-2 Inhibitors in Heart Failure: Current Management, Unmet Needs, and Therapeutic Prospects. J Am Heart Assoc. 2019;8(20):e013389. doi:10.1161/JAHA.119.013389.Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-28. doi:10.1056/NEJMoa1504720.Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-28. doi:10.1056/NEJMoa1504720.Wiviott SD, Raz I, Bonaca MP, et al. The design and rationale for the Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 Trial. Am Heart J. 2018;200:83-9. doi:10.1016/j.ahj.2018.01.012.Wiviott SD, Raz I, Bonaca MP, et al. The design and rationale for the Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 Trial. Am Heart J. 2018;200:83-9. doi:10.1016/j.ahj.2018.01.012.Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019;380(4):347-357. doi:10.1056/NEJMoa1812389.Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019;380(4):347-357. doi:10.1056/NEJMoa1812389.Kato ET, Silverman MG, Mosenzon O, et al. Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus. Circulation. 2019;139(22):2528-36. doi:10.1161/CIRCULATIONAHA.119.040130.Kato ET, Silverman MG, Mosenzon O, et al. Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus. Circulation. 2019;139(22):2528-36. doi:10.1161/CIRCULATIONAHA.119.040130.Инструкция по медицинскому применению лекарственного препарата Форсига. [Электронный ресурс]: 2019. URL: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=67d1645a-761c-4c4b-bdfd-daeec0493836&t= (дата обращения: 23.04.2020).Instructions for medical use of the drug of Forxiga. [Electronic resource] (In Russ.) 2019. URL: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=67d1645a-761c-4c4b-bdfd-daeec0493836&t= (дата обращения: 23.04.2020).McMurray JJV, Solomon SD, Inzucchi SE, 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.McMurray JJV, Solomon SD, Inzucchi SE, 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.McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004. doi:10.1056/NEJMoa1409077.McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004. doi:10.1056/NEJMoa1409077.Swedberg K, Komajda M, Bohm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;376(9744):875-85. doi:10.1016/S0140-6736(10)61198-1.Swedberg K, Komajda M, Bohm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;376(9744):875-85. doi:10.1016/S0140-6736(10)61198-1.Petrie MC, Verma S, Docherty KF, et al. Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes. JAMA. 2020 Mar 27. doi:10.1001/jama.2020.1906. [Epub ahead of print].Petrie MC, Verma S, Docherty KF, et al. Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes. JAMA. 2020 Mar 27. doi:10.1001/jama.2020.1906. [Epub ahead of print].Docherty KF, Jhund PS, Inzucchi SE, et al. Effects of dapagliflozin in DAPA-HF according to background heart failure therapy. Eur Heart J. 2020 Mar 28. pii: ehaa183. doi:101093/eurheartj/ehaa183. [Epub ahead of print].Docherty KF, Jhund PS, Inzucchi SE, et al. Effects of dapagliflozin in DAPA-HF according to background heart failure therapy. Eur Heart J. 2020 Mar 28. pii: ehaa183. doi:101093/eurheartj/ehaa183. [Epub ahead of print].Martinez FA, Serenelli M, Nicolau JC, et al. Efficacy and Safety of Dapagliflozin in Heart Failure With Reduced Ejection Fraction According to Age: Insights From DAPA-HF. Circulation. 2020;141(2):100-111. doi:10.1161/CIRCULATIONAHA.119.044133.Martinez FA, Serenelli M, Nicolau JC, et al. Efficacy and Safety of Dapagliflozin in Heart Failure With Reduced Ejection Fraction According to Age: Insights From DAPA-HF. Circulation. 2020;141(2):100-111. doi:10.1161/CIRCULATIONAHA.119.044133.Kosiborod MN, Jhund PS, Docherty KF, et al. Effects of Dapagliflozin on Symptoms, Function, and Quality of Life in Patients With Heart Failure and Reduced Ejection Fraction: Results From the DAPA-HF Trial. Circulation. 2020;141(2):90-9. doi:10.1161/CIRCULATIONAHA.119.044138.Kosiborod MN, Jhund PS, Docherty KF, et al. Effects of Dapagliflozin on Symptoms, Function, and Quality of Life in Patients With Heart Failure and Reduced Ejection Fraction: Results From the DAPA-HF Trial. Circulation. 2020;141(2):90-9. doi:10.1161/CIRCULATIONAHA.119.044138.Packer M, Anker SD, Butler J, et al. Effects of Sodium-Glucose Cotransporter 2 Inhibitors for the Treatment of Patients With Heart Failure: Proposal of a Novel Mechanism of Action. JAMA Cardiol. 2017;2(9):1025-9. doi:10.1001/jamacardio.2017.2275.Packer M, Anker SD, Butler J, et al. Effects of Sodium-Glucose Cotransporter 2 Inhibitors for the Treatment of Patients With Heart Failure: Proposal of a Novel Mechanism of Action. JAMA Cardiol. 2017;2(9):1025-9. doi:10.1001/jamacardio.2017.2275.Verma S, McMurray JJV, Cherney DZI. The Metabolodiuretic Promise of Sodium-Dependent Glucose Cotransporter 2 Inhibition: The Search for the Sweet Spot in Heart Failure. JAMA Cardiol. 2017;2(9):939-40. doi:10.1001/jamacardio.2017.1891.Verma S, McMurray JJV, Cherney DZI. The Metabolodiuretic Promise of Sodium-Dependent Glucose Cotransporter 2 Inhibition: The Search for the Sweet Spot in Heart Failure. JAMA Cardiol. 2017;2(9):939-40. doi:10.1001/jamacardio.2017.1891.Wojcik C, Warden B. Mechanisms and Evidence for Heart Failure Benefits from SGLT2 Inhibitors. Curr Cardiol Rep. 2019;21(10):130. doi:10.1007/s11886-019-1219-4.Wojcik C, Warden B. Mechanisms and Evidence for Heart Failure Benefits from SGLT2 Inhibitors. Curr Cardiol Rep. 2019;21(10):130. doi:10.1007/s11886-019-1219-4.CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med. 1987 Jun 4;316(23): 1429-35. doi:10.1056/NEJM198706043162301.CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med. 1987 Jun 4;316(23): 1429-35. doi:10.1056/NEJM198706043162301.Beggs S, Gardner R. Thirty years of heart failure. Eur Heart J. 2018;39(10):824-6. doi:10.1093/eurheartj/ehy051.Beggs S, Gardner R. Thirty years of heart failure. Eur Heart J. 2018;39(10):824-6. doi:10.1093/eurheartj/ehy051.Machaj F, Dembowska E, Rosik J, et al. New therapies for the treatment of heart failure: a summary of recent accomplishments. Ther Clin Risk Manag. 2019;15:147-55. doi:10.2147/TCRM.S179302.Machaj F, Dembowska E, Rosik J, et al. New therapies for the treatment of heart failure: a summary of recent accomplishments. Ther Clin Risk Manag. 2019;15:147-55. doi:10.2147/TCRM.S179302.Jones NR, Hobbs FR, Taylor CJ. Prognosis following a diagnosis of heart failure and the role of primary care: a review of the literature. BJGP Open. 2017;1(3):bjgpopen17X101013. doi:10.3399/bjgpopen17X101013.Jones NR, Hobbs FR, Taylor CJ. Prognosis following a diagnosis of heart failure and the role of primary care: a review of the literature. BJGP Open. 2017;1(3):bjgpopen17X101013. doi:10.3399/bjgpopen17X101013.Li H, Hastings MH, Rhee J, et al. Targeting Age-Related Pathways in Heart Failure. Circ Res. 2020;126(4):533-51. doi:10.1161/CIRCRESAHA.119.315889.Li H, Hastings MH, Rhee J, et al. Targeting Age-Related Pathways in Heart Failure. Circ Res. 2020;126(4):533-51. doi:10.1161/CIRCRESAHA.119.315889.Фомин И. В. Хроническая сердечная недостаточность в Российской Федерации: что сегодня мы знаем и что должны делать. Российский кардиологический журнал. 2016;(8):7-13. doi:1015829/1560-4071-2016-8-7-13.Fomin IV. Chronic heart failure in Russian Federation: what do we know and what to do. Russian Journal of Cardiology. 2016;(8):7-13. (In Russ.) doi:1015829/1560-4071-2016-8-7-13.Wastesson JW, Morin L, Tan ECK, Johnell K. An update on the clinical consequences of polypharmacy in older adults: a narrative review. Expert Opin Drug Saf. 2018;17(12):1185-96. doi:10.1080/14740338.2018.1546841.Wastesson JW, Morin L, Tan ECK, Johnell K. An update on the clinical consequences of polypharmacy in older adults: a narrative review. Expert Opin Drug Saf. 2018;17(12):1185-96. doi:10.1080/14740338.2018.1546841.Nassif ME, Windsor SL, Tang F, et al. Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction: The DEFINE-HF Trial. Circulation. 2019;140(18):1463-76. doi:10.1161/CIRCULATIONAHA.119.042929.Nassif ME, Windsor SL, Tang F, et al. Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction: The DEFINE-HF Trial. Circulation. 2019;140(18):1463-76. doi:10.1161/CIRCULATIONAHA.119.042929.Lewis EF, Claggett BL, McMurray JJ, et al. Health-related quality of life outcomes in PARADIGM-HF. Circ Heart Fail. 2017;10(8):pii: e003430. doi:10.1161/CIRCHEARTFAILURE.116.003430.Lewis EF, Claggett BL, McMurray JJ, et al. Health-related quality of life outcomes in PARADIGM-HF. Circ Heart Fail. 2017;10(8):pii: e003430. doi:10.1161/CIRCHEARTFAILURE.116.003430.McMurray JJV, DeMets DL, Inzucchi SE, et al. A trial to evaluate the effect of the sodium-glucose co-transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA-HF). Eur J Heart Fail. 2019;21(5):665-75. doi:10.1002/ejhf.1432.McMurray JJV, DeMets DL, Inzucchi SE, et al. A trial to evaluate the effect of the sodium-glucose co-transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA-HF). Eur J Heart Fail. 2019;21(5):665-75. doi:10.1002/ejhf.1432.Treatment for Heart Failure: Endpoints for Drug Development. Guidance for Industry [Electronic resource] [Электронный ресурс]: 06.2019. URL: https://www.fda.gov/media/128372/download (дата обращения: 16.04.2020).Treatment for Heart Failure: Endpoints for Drug Development. Guidance for Industry [Electronic resource] [Электронный ресурс]: 06.2019. URL: https://www.fda.gov/media/128372/download (дата обращения: 16.04.2020).

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