DOI: https://doi.org/10.24959/cphj.20.1525

Conservative therapy of chronic heart failure: glyflosins destroy the worldview

I. G. Kravchenko, Yu. S. Rudyk, O. O. Medentseva, M. E. Chernenok

Abstract


Medications representing a new class of drugs – inhibitors of sodium-glucose transport protein type 2 (SGLT2 inhibitors, gliflozins) have appeared in the clinical practice relatively recently. Now they are a new hope for the treatment of chronic heart failure (HF) in patients with/without type 2 diabetes mellitus (DM2). The article briefly discusses the main mechanisms of action of gliflozins, which allowed their active use in clinical practice, in particular, the ability of gliflosins to affect the size and the functional activity of epicardial adipose tissue, as well as the state of the sympathetic nervous system, thereby preventing the development of HF. The main results of the large-scale randomized clinical trials, such as CANVAS, CREDENCE, EMPA, EMPAREG OUTCOME, DECLARE-TIMI 58 are presented. They analyze the effects of canagliflozin, empagliflozin, dapagliflozin on various cardiovascular outcomes: cardiovascular death, myocardial infarction, nonfatal stroke, HF, frequency of hospitalizations caused by HF. Modern concepts of the probable mechanisms of the cardioprotective action of gliflozins are given. The results of meta-analyses revealing the possibility of including gliflozins in the treatment of HF, DM2, as well as those who studied the cardiovascular safety of this drugs have been analyzed. The results of a recently published international trial DAPAHF studied the cardioprotective properties of dapagliflozin in HF, have been considered. The unique pleotropic cardiovascular properties of SGLT2 inhibitors (dapagliflozin) and their ability to prevent the progression of HF and reduce cardiovascular mortality allow us to hope that these drugs have a specific cardioprotective activity with respect to the treatment of HF with the reduced and preserved ejection fraction. Glyflosins, particularly dapagliflozine, are believed to be the fifth class of drugs recommended for the treatment of CH withthe reduced left volume ejection fraction, regardless of the presence or absence of DM2.

Conclusions. It is expected that the results of the new studies will demonstrate the additional advantages of SGLT2 inhibitors in patients with and without cardiovascular diseases, CH with and without of DM2 and will help to better understand the mechanisms of their action, change approaches to the treatment of many patients.

Keywords


cardiac insufficiency; gliflozins; dapagliflozin; cardioprotective mechanism; new indication for administration

References


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GOST Style Citations


1.    Giugliano, D. Class effect for SGLT-2 inhibitors: a tale of 9 drugs / D. Giugliano, K. Esposito // Cardiovasc. Diabetol. – 2019. – № 18. – P. 94. https://doi.org/10.1186/s12933-019-0899-9 

 

2.    Effects of DAPAgliflozin on CARDiac substrate uptake, myocardial efficiency, and myocardial contractile work in type 2 diabetes patients – a description of the DAPACARD study / A. Akerbloma, J. Oldgren, A. Latva-Rasku et al. // Upsala J. of Med. Sci. – 2019. – № 124. – P . 59–64. https://doi.org/10.1080/03009734.2018.1515281 

 

3.    Patel, D. K. The Pleiotropic Effects of Sodium–Glucose Cotransporter-2 Inhibitors: Beyond the Glycemic Benefit / D. K. Patel, J. Strong // Diabetes Ther. – 2019. – № 10. – P. 1771–1792. https://doi.org/10.1007/s13300-019-00686-z 

 

4.    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) / J. J. V. McMurray, D. L. DeMets, S. E. Inzucchi et al. // Eur. J. Heart Fail. – 2019. – № 21. – P. 665–675. https://doi.org/10.1002/ejhf.1432 

 

5.    Dapagliflozin and cardiovascular outcomes in type 2 diabetes / S. D. Wiviott, I. Raz, M. P. Bonaca et al. // N. Engl. J. Med. – 2019. – № 380. – P. 347–357. https://doi.org/10.1056/nejmoa1812389 

 

6.    The design and rationale for the Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 Trial / S. D. Wiviott, I. Raz, M. P. Bonaca et al. // Am. Heart J. – 2018. – № 200. – P. 83–89. https://doi.org/10.1016/j.ahj.2018.01.012 

 

7.    Olgar, Y. A sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin comparison with insulin shows important effects on Zn2+-transporters in cardiomyocytes from insulin-resistant metabolic syndrome rats through inhibition of oxidative stress / Y. Olgar, B. Turan // Can. J. Physiol. Pharmacol. – 2019. – № 97. – P. 528–535. https://doi.org/10.1139/cjpp-2018-0466 

 

8.    Canagliflozin inhibits interleukin-1β-stimulated cytokine and chemokine secretion in vascular endothelial cells by AMP-activated protein kinase-dependent and -independent mechanisms / S. J. Mancini, D. Boyd, O. J. Katwan et al. // Sci. Rep. – 2018. – № 8. – P. 52–76. https://doi.org/10.1038/s41598-018-23420-4 

 

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12.  Effects of dapagliflozin on human epicardial adipose tissue: modulation of insulin resistance, inflammatory chemokine production, and differentiation ability / E. Dıaz-Rodrıguez, R. M. Agra, F. Fernandez et al. // Cardiovasc. Res. – 2018. – № 114. – P. 336–346. https://doi.org/10.1093/cvr/cvx186 

 

13.  The effect of dapagliflozin treatment on epicardial adipose tissue volume / T. Sato, Y. Aizawa, S. Yuasa et al. // Cardiovasc. Diabetol. – 2018. – № 17. – P. 6. https://doi.org/10.1186/s12933-017-0658-8 

 

14.  Meta-Analysis of Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Cardiovascular Outcomes and All-Cause Mortality Among Patients With Type 2 Diabetes Mellitus / H. Tang, Z. Fang, T. Wang et al. // Am. J. Cardiol. – 2016. – № 118. – P. 1774–1780. https://doi.org/10.1016/j.amjcard.2016.08.061 

 

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19.  Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction / J. J. V. McMurray, S. D. Solomon, S. E. Inzucchi et al. // N. Engl. J. Med. – 2019. – № 381. – P. 1995–2008. https://doi.org/10.1056/nejmoa1911303 





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Abbreviated key title: Clin. pharm.

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