New opportunities for chronic heart failure patients’ treatment: focus at dapagliflosin

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Chronic heart failure (CHF) still occupies a leading position in the structure of hospitalizations and mortality of patients. Studies of approaches to the treatment of this disease remains to be an urgent problem in the spectrum of attention of the medical community. Inhibitors of sodium-glucose cotransporter type 2 (IGLT-2), originally developed for the treatment of type 2 diabetes mellitus, in recent years are one of the most studied classes of medicines that have proven their efficacy in CHF treatment. Current article describes studied pharmacological mechanisms of iSGLT-2 action, presents an analysis of clinical studies on the use of this class of drugs in patients with CHF. The main attention is paid to the analysis of the DELIVER study, the results of which demonstrated the efficacy of dapagliflozin in treatment of heart failure patients with a moderately reduced and preserved left ventricular ejection fraction.

Full Text

Restricted Access

About the authors

Valentin V. Malimon

N.I. Pirogov Russian National Research Medical University of the Ministry of Healthcare of Russia

Author for correspondence.
Email: malimon.1993@mail.ru
ORCID iD: 0009-0006-2808-0956

assistant at the Department of hospital therapy named after academician P.E. Lukomsky of the Faculty of general medicine

Russian Federation, Moscow

Valentin A. Kokorin

N.I. Pirogov Russian National Research Medical University of the Ministry of Healthcare of Russia

Email: valentinkokorin@yahoo.com
ORCID iD: 0000-0001-8614-6542

MD, associate Professor, professor of the Department of hospital therapy named after academician P.E. Lukomsky of the Faculty of general medicine

Russian Federation, Moscow

References

  1. Savarese G., Lund L.H. Global Public Health Burden of Heart Failure. Card Fail Rev. 2017; 3(1): 7–11. https://dx.doi.org/10.15420/cfr.2016:25:2.
  2. Kovalenko E.V., Lozhkina M.V., Arabidze G.G., Kryakushkin V.G. Efficacy of sodium-glucose co-transporter-2 inhibitors in patients with heart failure. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2021; 26(1): 158–165 (In Russ.), https://dx.doi.org/10.15829/1560-4071-2021-4235. EDN: JRTGGQ.
  3. Беленков Ю.Н., Мареев В.Ю., Агеев Ф.Т. и др. Истинная распространенность ХСН в европейской части Российской Федерации (исследование ЭПОХА, госпитальный этап). Журнал Сердечная Недостаточность. 2011; 12(2): 63–68. [Belenkov Yu.N., Mareev V.Yu., Ageev F.T. et al. True prevalence of CHF in the European part of the Russian Federation (EPOCHA study, hospital stage). Zhurnal Serdechnaya Nedostatochnost’ = Journal of Heart Failure. 2011; 12(2): 63–68 (In Russ.). EDN: OZDQTR.
  4. Mareev V.Yu., Fomin I.V., Ageev F.T. et al. Clinical recommendations of OSSN–RCO–RSMSIM. Heart failure: Chronic (CHF) and acute decompensated (CHF). Diagnosis, prevention and treatment. Kardiologiya = Cardiology. 2018; 58(6S): 8–158 (In Russ.)]. https://dx.doi.org/ 10.18087/cardio.2475. EDN: XUAREL.
  5. Mareev V.Yu., Belenkov Yu.N. Chronic heart failure and non-insulin-dependent diabetes mellitus random relationship or pattern. Terapevticheskiy arkhiv = Therapeutic Archive. 2003; 75(10): 1–10 (In Russ.) EDN: OKJQPZ.
  6. Khasanov N.R. Effects of SGLT2 inhibitor dapagliflozin in patients with heart failure with reduced ejection fraction. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2020; 25(8): 83–90 (In Russ.). https://dx.doi.org/10.15829/1560-4071-2020-4049. EDN: TUXNKK.
  7. Zinman B., Wanner C., Lachin J.M., et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015; 373(22): 2117–28. https://dx.doi.org/10.1056/NEJMoa1504720.
  8. Neal B., Perkovic V., Mahaffey K.W. et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017; 377(21): 644–57. https://dx.doi.org/ 10.1056/NEJMoa1611925.
  9. 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. https://dx.doi.org/10.1056/NEJMoa1812389.
  10. 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. https://dx.doi.org/10.2337/dci19-0074.
  11. Kalra S., Jain A., Ved J., Unnikrishnan A.G. Sodium glucose cotransporter 2 inhibition and health benefits: The Robin Hood effect. Indian J Endocrinol Metab. 2016; 20(5): 725–29. https://dx.doi.org/10.4103/22308210.183826.
  12. Verma S., McMurray J.J.V., Cherney D.Z.I. 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. https://dx.doi.org/10.1001/jamacardio.2017.1891.
  13. Sattar N., McLaren J., Kristensen S.L. et al. SGLT2 inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms? Diabetologia. 2016; 59(7): 1333–39. https://dx.doi.org/10.1007/s00125-016-3956-x.
  14. Brown A.J.M., Lang C., McCrimmon R., Struthers A. Does dapagliflozin regress left ventricular hypertrophy in patients with type 2 diabetes? A prospective, double-blind, randomised, placebo-controlled study. BMC Cardiovasc Disord. 2017; 17(1): 229. https://dx.doi.org/10.1186/s12872-017-0663-6.
  15. Natali A., Nesti L., Fabiani I. et al. Impact of empagliflozin on subclinical left ventricular dysfunctions and on the mechanisms involved in myocardial disease progression in type 2 diabetes: rationale and design of the EMPA-HEART trial. Cardiovasc Diabetol. 2017; 16(1): 130. https://dx.doi.org/10.1186/s12933-017-0615-6.
  16. Singh J.S., Fathi A., Vickneson K. et al. Research into the effect of SGLT2 inhibition on left ventricular remodelling in patients with heart failure and diabetes mellitus (REFORM) trial rationale and design. Cardiovasc Diabetol. 2016; 15: 97. https://dx.doi.org/10.1186/s12933-016-0419-0.
  17. Verma S., Mazer C.D., Yan A.T. et al. EMPA-HEART Cardiolink-6 trial: A randomized trial evaluating the effect of empagliflozin on left ventricular structure, function and biomarkers in people with type 2 diabetes (T2D) and coronary heart disease. Сirculation. 2018; 138(25): A19332. https://dx.doi.org/10.1161/CIRCULATIONAHA.119.042375.
  18. Brown A.J.M., Gandy S., McCrimmon R. et al. A randomized controlled trial of dapagliflozin on left ventricular hypertrophy in people with type two diabetes: The DAPA-LVH trial. Eur Heart J. 2020; 41(36): 3421–32. https://dx.doi.org/10.1093/eurheartj/ehaa419.
  19. Fedak P.W., Verma S., Weisel R.D., Li R.K. Cardiac remodeling and failure from molecules to man (part II). Cardiovasc Pathol. 2006; 14(2): 49–60. https://dx.doi.org/10.1016/j.carpath.2005.01.005.
  20. Lee T.M., Chang N.C., Lin S.Z. Dapagliflozin, a selective SGLT2 inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts. Free Radic Biol Med. 2017; 104: 298–310. https://dx.doi.org/10.1016/j.freeradbiomed.2017.01.035.
  21. Patel V.B., Shah S., Verma S., Oudit G.Y. Epicardial adipose tissue as a metabolic transducer: role in heart failure and coronary artery disease. Heart Fail Rev. 2017; 22(6): 889–902. https://dx.doi.org/10.1007/s10741-017-9644-1.
  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. https://dx.doi.org/10.1186/s12933-017-0658-8.
  23. 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. https://dx.doi.org/10.1007/s00125-018-4670-7.
  24. Bers D.M. Cardiac sarcoplasmic reticulum calcium leak: basis and roles in cardiac dysfunction. Annu Rev Physiol. 2014; 76: 107–27. https://dx.doi.org/10.1146/annurev-physiol-020911-153308.
  25. Packer M., Anker S.D., 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): 1025–29. https://dx.doi.org/10.1001/jamacardio.2017.2275.
  26. Uthman L., Baartscheer A., Bleijlevens B. et al. Class effects of SGLT2 inhibitors in mouse cardiomyocytes and hearts: inhibition of Na+/H+ exchanger, lowering of cytosolic Na+ and vasodilation. Diabetologia. 2018; 61(3): 722–26. https://dx.doi.org/10.1007/s00125-017-4509-7.
  27. Baartscheer A., Schumacher C.A., Wust R.C. et al. Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+/H+ exchanger in rats and rabbits. Diabetologia. 2017; 60(3): 568–73. https://dx.doi.org/10.1007/s00125-016-4134-x.
  28. Liu T., Takimoto E., Dimaano V.L. et al. Inhibiting mitochondrial Na+/Ca2+ exchange prevents sudden death in a guinea pig model of heart failure. Circ Res. 2014; 115(1): 44–54. https://dx.doi.org/10.1161/CIRCRESAHA.115.303062.
  29. Gallo L.A., Wright E.M., Vallon V. Probing SGLT2 as a therapeutic target for diabetes: Basic physiology and consequences. Diab Vasc Dis Res. 2015; 12(2): 78–89. https://dx.doi.org/10.1177/1479164114561992.
  30. Lopaschuk G.D., Ussher J.R., Folmes C.D. et al. Myocardial fatty acid metabolism in health and disease. Physiol Rev. 2010; 90(1): 207–58. https://dx.doi.org/10.1152/physrev.00015.2009.
  31. Ferrannini E., Mark M., Mayoux E. CV protection in the EMPA-REG OUTCOME trial: a “thrifty substrate” hypothesis. Diabetes Care. 2016; 39: 1108–14. https://dx.doi.org/ 10.2337/dc16-0330.
  32. Mizuno Y., Harada E., Nakagawa H. et al. The diabetic heart utilizes ketone bodies as an energy source. Metabolism. 2017; 77: 65–72. https://dx.doi.org/10.1016/j.metabol.2017.08.005.
  33. Gormsen L.C., Svart M., Thomsen H.H. et al. Ketone body infusion with 3-hydroxybutyrate reduces myocardial glucose uptake and increases blood flow in humans: A positron emission tomography study. J Am Heart Assoc. 2017; 6(3): e005066. https://dx.doi.org/10.1161/JAHA.116.005066.
  34. Stowe K.A., Burgess S.C., Merritt M. et al. Storage and oxidation of long-chain fatty acids in the C57/BL6 mouse heart as measured by NMR spectroscopy. FEBS Lett. 2006; 580(17): 4282–87. https://dx.doi.org/10.1016/j.febslet.2006.06.068.
  35. Cannon C.P., Pratley R., Dagogo-Jack S. et al. Cardiovascular outcomes with ertugliflozin in type 2 diabetes. N Engl J Med. 2020; 383(15): 1425–35. https://dx.doi.org/10.1056/NEJMoa2004967.
  36. 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. https://dx.doi.org/10.1056/NEJMoa1911303.
  37. Shulkina S.G., Kokorin V.A. New perspectives and real possibilities in the treatment of patients with heart failure. Terapiya = Therapy. 2021; 7(6): 91–97 (In Russ.). https://dx.doi.org/10.18565/therapy.2021.6.91-97. EDN: GRZPOK.
  38. McDonagh T.A., Metra M., Adamo M. et al.; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021; 42(36): 3599–726. https://dx.doi.org/10.1093/eurheartj/ehab368.
  39. Tereshchenko S.N., Galyavich A.S., Uskach T.M. et al. 2020 clinical practice guidelines for chronic heart failure. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2020; 25(11): 311–374 (In Russ.). https://dx.doi.org/10.15829/1560-4071-2020-4083. EDN: LJGGQV.
  40. Heidenreich P.A., Bozkurt B., Aguilar D. et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022; 145(18): e895–e1032. https://dx.doi.org/10.1161/CIR.0000000000001063.
  41. Packer M., Anker S.D., Butler J., et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020; 383(15): 1413–24. https://dx.doi.org/ 10.1056/NEJMoa2022190.
  42. Bhatt D.L., Szarek M., Steg P.G. et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med. 2021; 384(2): 117–28. https://dx.doi.org/10.1056/NEJMoa2030183.
  43. Anker S.D., Butler J., Filippatos G. et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021; 385(16): 1451–61. https://dx.doi.org/10.1056/NEJMoa2107038.
  44. Solomon S.D., McMurray J.J.V., Claggett B. et al.; DELIVER Trial Committees and Investigators. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022; 387(12): 1089–98. https://dx.doi.org/10.1056/NEJMoa2206286.
  45. Cunningham J.W., Vaduganathan M., Claggett B.L. et al. Dapagliflozin in patients recently hospitalized with heart failure and mildly reduced or preserved ejection fraction. J Am Coll Cardiol. 2022; 80(14): 1302–10. https://dx.doi.org/10.1016/j.jacc.2022.07.021.
  46. 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. https://dx.doi.org/10.1056/NEJMoa2024816.
  47. Voors A.A., Angermann C.E., Teerlink J.R. et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: A multinational randomized trial. Nat Med. 2022; 28(3): 568–74. https://dx.doi.org/0.1038/s41591-021-01659-1.
  48. Bhatt A.S., Varshney A.S., Nekoui M. et al. Virtual optimization of guideline-directed medical therapy in hospitalized patients with heart failure with reduced ejection fraction: The IMPLEMENT-HF pilot study. Eur J Heart Fail. 2021; 23(7): 1191–201. https://dx.doi.org/10.1002/ejhf.2163.
  49. Greene S.J., Butler J., Albert N.M. et al. Medical therapy for heart failure with reduced ejection fraction. J Am Coll Cardiol. 2018; 72(4): 351–66. https://dx.doi.org/10.1016/j.jacc.2018.04.070.
  50. Gattis W.A., O’Connor C.M., Gallup D.S. et al. Predischarge initiation of carvedilol in patients hospitalized for decompensated heart failure: results of the initiation management predischarge: Process for assessment of carvedilol therapy in heart failure (IMPACT-HF) trial. J Am Coll Cardiol. 2004; 43(9): 1534–41. https://dx.doi.org/10.1016/j.jacc.2003.12.040.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2023 Bionika Media

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies