Статья
Эффекты применения ингибитора натрий-глюкозного котранспортера 2 типа дапаглифлозина у пациентов с сердечной недостаточностью с низкой фракцией выброса левого желудочка
Ингибиторы натрий-глюкозного котранспортера 2 типа продемонстрировали способность снижать риск сердечно-сосудистых событий, развития и декомпенсаций сердечной недостаточности (СН) у пациентов с сахарным диабетом 2 типа (СД2). Улучшение прогноза СН может быть обусловлено не только сахароснижающим эффектом этого класса препаратов. В исследовании DAPA-HF у пациентов с СН с низкой фракцией выброса было продемонстрировано преимущество дапаглифлозина в снижении частоты сердечно-сосудистой смерти, ухудшения течения СН, улучшение симптомов СН по сравнению с плацебо, независимо от наличия СД2 и проводимой рекомендованной базовой терапии СН.
1. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015; 373:2117-28. doi:10.1056/NEJMoa1504720.
2. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644-57. doi:10.1056/NEJMoa1611925.
3. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380:347-57. doi:10.1056/NEJMoa1812389.
4. 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;2:1025-9. doi:10.1001/jamacardio.2017.2275.
5. Verma S, McMurray JJV. SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia. 2018;61:2108-17. doi:10.1007/s00125-0184670-7.
6. Inzucchi SE, Kosiborod M, Fitchett D, et al. Improvement in cardiovascular outcomes with empagliflozin is independent of glycemic control. Circulation. 2018;138:1904-7. doi:10.1161/CIRCULATIONAHA.118.035759.
7. Lytvyn Y, Bjornstad P, Udell JA, et al. Sodium glucose cotransporter-2 inhibition in heart failure: potential mechanisms, clinical applications, and summary of clinical trials. Circulation. 2017;136:1643-58. doi:10.1161/CIRCULATIONAHA.117.030012.
8. Bonnet F, Scheen AJ. Effects of SGLT2 inhibitors on systemic and tissue low-grade inflammation: the potential contribution to diabetes complications and cardiovascular disease. Diabetes Metab. 2018;44:457-64. doi:10.1016/j.diabet.2018.09.005.
9. Heerspink HJL, de Zeeuw D, Wie L, et al. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes, obesity & metabolism. 2013;15(9):853-62. doi:10.1111/dom.12127.
10. DeFronzo RA, Norton L, Abdul-Ghani M. Renal, metabolic and cardiovascular considerations of SGLT2 inhibition. Nat Rev Nephrol. 2017;13:11-26. doi:10.1038/nrneph.2016.170.
11. Abdul-Ghani MA, DeFronzo RA, Norton L. Novel hypothesis to explain why SGLT2 inhibitors inhibit only 30–50% of filtered glucose load in humans. Diabetes. 2013;62:3324-8. doi:10.2337/db13-0604.
12. Rahman A, Fujisawa Y, Nakano D, et al. Effect of a selective SGLT2 inhibitor, luseogliflozin, on circadian rhythm of sympathetic nervous function and locomotor activities in metabolic syndrome rats. Clin Exp Pharmacol Physiol. 2017;44:522-5. doi:10.1111/1440-1681.12725.
13. Wan N, Rahman A, Hitomi H, Nishiyama A. The Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Sympathetic Nervous Activity. Front. Endocrinol. (Lausanne) 2018;9:421. doi:10.3389/fendo.2018.00421.
14. Herat LY, Magno AL, Rudnicka C, et al. SGLT2 Inhibitor-Induced Sympathoinhibition: A Novel Mechanism for Cardiorenal Protection. JACC Basic Transl Sci. 2020;5(2):169-79. doi:10.1016/j.jacbts.2019.11.007.
15. Seferović PM, Fragasso G, Petrie M, et al. Sodium glucose co-transporter-2 inhibitors in heart failure: beyond glycaemic control. The Position Paper of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2020; Jul 2. doi:10.1002/ejhf.1954.
16. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;21:1995-2008. doi:10.1056/NEJMoa1911303.
17. Seman L, Macha S, Nehmiz G, et al. Empagliflozin (BI 10773), a potent and selective SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects. Clin Phamac in Drug Dev. 2013;2(2):152-61. doi:10.1002/cpdd.16.
18. Verma S, McMurray JJV, Cherney DZI. The metabolodiuretic promise of sodiumdependent glucose cotransporter 2 inhibition: the search for the sweet spot in heart failure. JAMA Cardiol. 2017;2:939-40. doi:10.1001/jamacardio.2017.1891.
19. Sattar N, McLaren J, Kristensen SL, et al. SGLT2 inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms? Diabetologia. 2016;59:1333-9. doi:10.1007/s00125-016-3956-x.
20. Ferrannini E, Mark M, Mayoux E. CV protection in the EMPA-REG OUTCOME trial: a “thrifty substrate” hypothesis. Diabetes Care. 2016;39:1108-14. doi:10.2337/dc16-0330.
21. Mudaliar S, Alloju S, Henry RR. Can a shift in fuel energetics explain the beneficial cardiorenal outcomes in the EMPA-REG OUTCOME study? A unifying hypothesis. Diabetes Care. 2016;39:1115-22. doi:10.2337/dc16-0542.
22. Heerspink HJL, et al. Renoprotective effects of sodium-glucose cotransporter-2 inhibitors. Kidney Int. 2018;94(1):26-39. doi:10.1016/j.kint.2017.12.027.
23. 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.
24. Karg MV, Bosch A, Kannenkeril D, et al. SGLT-2-inhibition with dapagliflozin reduces tissue sodium content: a randomized controlled trial. Cardiovasc Diabetol. 2018;17:5. doi:10.1186/s12933-017-0654-z.
25. 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):722-6. doi:10.1007/s00125-017-4509-7.
26. Hallow KM, Helmlinger G, Greasley PJ, et al. Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis. Diabetes 2018; Obes Metab. 20:479-87. doi:10.1111/dom.13126.
27. Ott C, Jumar A, Striepe K, et al. A randomised study of the impact of the SGLT2 inhibitor dapagliflozin on microvascular and macrovascular circulation. Cardiovasc Diabetol. 2017;16:26. doi:10.1186/s12933-017-0510-1.
28. Pfeifer M, Townsend RR, Davies MJ, et al. Effects of canagliflozin, a sodium glucose cotransporter 2 inhibitor, on blood pressure and markers of arterial stiffness in patients with type 2 diabetes mellitus: a post hoc analysis. Cardiovasc Diabetol. 2017;16:29. doi:10.1186/s12933-017-0511-0.
29. Solini A, Giannini L, Seghieri M, et al. Dapagliflozin acutely improves endothelial dysfunction, reduces aortic stiffness and renal resistive index in type 2 diabetic patients: a pilot study. Cardiovasc Diabetol. 2017;16(1):138. doi:10.1186/s12933-017-0621-8.
30. Brown AJM, Lang C, McCrimmon R, Struthers A. Does dapagliflozin regress left ventricular hypertrophy in patients with type 2 diabetes? A prospective, double-blind, randomised, placebocontrolled study. BMC Cardiovasc Disord. 2017;17:229. doi:10.1186/s12872017-0663-6.
31. 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;16:130. doi:10.1186/s12933-017-0615-6.
32. Singh JS, 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. doi:10.1186/s12933-0160419-0.
33. Verma S, Mazer CD, Yan AT, 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. doi:10.1161/CIRCULATIONAHA.119.042375.
34. Brown AJM, 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;00:1-12, Jun 24;ehaa419. doi:10.1093/eurheartj/ehaa419.
35. Fedak PW, Verma S, Weisel RD, Li RK. Cardiac remodeling and failure from molecules to man (part II). Cardiovasc Pathol. 2006;14:49-60. doi:10.1016/j.carpath.2005.01.005.
36. Lee TM, Chang NC, Lin SZ. 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. doi:10.1016/j.freeradbiomed.2017.01.035.
37. Patel VB, Shah S, Verma S, Oudit GY. Epicardial adipose tissue as a metabolic transducer: role in heart failure and coronary artery disease. Heart Fail Rev. 2017;22:889-902. doi:10.1007/s10741-017-9644-1.
38. 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.
39. Garvey WT, Van Gaal L, Leiter LA, et al. Effects of canagliflozin versus glimepiride on adipokines and inflammatory biomarkers in type 2 diabetes. Metabolism. 2018;85:32-7. doi:10.1016/j.metabol.2018.02.002.
40. Bers DM. Cardiac sarcoplasmic reticulum calcium leak: basis and roles in cardiac dysfunction. Annu Rev Physiol. 2014;76:107-27. doi:10.1146/annurevphysiol-020911-153308.
41. Baartscheer A, Schumacher CA, Wust RC, et al. Empagliflozin decreases myocardial cytoplasmic Na + through inhibition of the cardiac Na+ /H + exchanger in rats and rabbits. Diabetologia. 2017;60:568-73. doi:10.1007/s00125-016-4134-x.
42. Liu T, Takimoto E, Dimaano VL, et al. Inhibiting mitochondrial Na+ /Ca 2+ exchange prevents sudden death in a guinea pig model of heart failure. Circ Res. 2014;115:44-54. doi:10.1161/CIRCRESAHA.115.303062.
43. Gallo LA, Wright EM, Vallon V. Probing SGLT2 as a therapeutic target for diabetes: basic physiology and consequences. Diab Vasc Dis Res. 2015;12:78-89. doi:10.1177/1479164114561992.
44. Lopaschuk GD, Ussher JR, Folmes CD, et al. Myocardial fatty acid metabolism in health and disease. Physiol Rev. 2010;90:207-58. doi:10.1152/physrev.00015.2009.
45. Mizuno Y, Harada E, Nakagawa H, et al. The diabetic heart utilizes ketone bodies as an energy source. Metabolism. 2017;77:65-72. doi:10.1016/j.metabol.2017.08.005.
46. Gormsen LC, Svart M, Thomsen HH, 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. doi:10.1161/JAHA.116.005066.
47. Stowe KA, Burgess SC, 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;580:4282-7. doi:10.1016/j.febslet.2006.06.068.
48. Wende AR, Brahma MK, McGinnis GR, Young ME. Metabolic Origins of Heart Failure. JACC: basic to translational science. 2017;2(3):297-310. doi:10.1016/j.jacbts.2016.11.009.
49. McMurray JJV, DeMets DL, Inzucchi SE, et al. A trial to evaluate the effect of the sodiumglucose co-transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA-HF). European Journal of Heart Failure. 2019;21:665-75. doi:10.1002/ejhf.1432.
50. McMurray JJV, 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.
51. Docherty KF, Jhund PS, Inzucchi SE, et al. Effects of dapagliflozin in DAPA-HF according to background heart failure therapy. European Heart Journal. 2020;0:1-14. doi:10.1093/eurheartj/ehaa183.
52. Greene SJ, Butler J, Albert NM, et al. Medical Therapy for Heart Failure With Reduced Ejection Fraction. J Am Coll Cardiol. 2018;72(4):351-66. doi:10.1016/j.jacc.2018.04.070.
53. Инструкция по медицинскому применению лекарственного препарата Форсига® (таблетки, покрытые пленочной оболочкой, 5 мг,10 мг). Регистрационное удостоверение № ЛП 002596 от 21.08.2014.