SGLT2 inhibitors: an evidence-based update on cardiovascular implications

References

• ElSayed NA, Aleppo G, Aroda VR, et al. Pharmacologic approaches to glycemic treatment: standards of Care in diabetes-2023. Diabetes Care. 2023 Jan 1;46(Suppl 1):S140–S157. doi: 10.2337/dc23-S009
   PubMedGoogle Scholar
• Samson SL, Vellanki P, Blonde L, et al. American Association of clinical endocrinology consensus statement: comprehensive type 2 diabetes management algorithm - 2023 Update. Endocr Pract. 2023 May;29(5):305–340. doi: 10.1016/j.eprac.2023.02.001
   PubMed Web of Science ®Google Scholar
• Vistisen D, Carstensen B, Patorno E, et al. Empagliflozin is associated with lower cardiovascular risk compared with dipeptidyl peptidase-4 inhibitors in adults with and without cardiovascular disease: EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study results from Europe and Asia. Cardiovascular Diabetology. 2023;22:233. doi: 10.1186/s12933-023-01963-9
   PubMed Web of Science ®Google Scholar
• Teo YN, Ting AZH, Teo YH, et al. Effects of Sodium/glucose cotransporter 2 (SGLT2) inhibitors and combined SGLT1/2 inhibitors on cardiovascular, metabolic, renal, and safety outcomes in patients with diabetes: a network meta-analysis of 111 randomized controlled trials. Am J Cardiovasc Drugs. 2022 May;22(3):299–323. doi: 10.1007/s40256-022-00528-7
   PubMed Web of Science ®Google Scholar
• Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356(24):2457–2471. doi: 10.1056/NEJMoa072761
   PubMed Web of Science ®Google Scholar
• Hiatt WR, Kaul S, Smith RJ. The cardiovascular safety of diabetes drugs–insights from the rosiglitazone experience. N Engl J Med. 2013 Oct 3;369(14):1285–1287. doi: 10.1056/NEJMp1309610
   PubMed Web of Science ®Google Scholar
• Byrne NJ, Parajuli N, Levasseur JL, et al. Empagliflozin prevents worsening of cardiac function in an experimental model of pressure overload-induced Heart failure. JACC Basic Transl Sci. 2017 Aug;2(4):347–354. doi: 10.1016/j.jacbts.2017.07.003
   PubMedGoogle Scholar
• Andreadou I, Efentakis P, Balafas E, et al. Empagliflozin limits myocardial infarction in vivo and cell death in vitro: role of STAT3, mitochondria, and redox aspects. Front Physiol. 2017;8:1077. doi: 10.3389/fphys.2017.01077
   PubMed Web of Science ®Google Scholar
• Shao Q, Meng L, Lee S, et al. Empagliflozin, a sodium glucose co-transporter-2 inhibitor, alleviates atrial remodeling and improves mitochondrial function in high-fat diet/streptozotocin-induced diabetic rats. Cardiovasc Diabetol. 2019 Nov 28;18(1):165. doi: 10.1186/s12933-019-0964-4
   PubMed Web of Science ®Google Scholar
• Aroor AR, Das NA, Carpenter AJ, et al. Glycemic control by the SGLT2 inhibitor empagliflozin decreases aortic stiffness, renal resistivity index and kidney injury. Cardiovasc Diabetol. 2018 Jul 30;17(1):108. doi: 10.1186/s12933-018-0750-8
   PubMedGoogle Scholar
• Quagliariello V, De Laurentiis M, Rea D, et al. The SGLT-2 inhibitor empagliflozin improves myocardial strain, reduces cardiac fibrosis and pro-inflammatory cytokines in non-diabetic mice treated with doxorubicin. Cardiovasc Diabetol. 2021 Jul 23;20(1):150. doi: 10.1186/s12933-021-01346-y
   PubMed Web of Science ®Google Scholar
• Sabatino J, De Rosa S, Tamme L, et al. Empagliflozin prevents doxorubicin-induced myocardial dysfunction. Cardiovasc Diabetol. 2020 May 15;19(1):66. doi: 10.1186/s12933-020-01040-5
   PubMed Web of Science ®Google Scholar
• Lahnwong S, Palee S, Apaijai N, et al. Acute dapagliflozin administration exerts cardioprotective effects in rats with cardiac ischemia/reperfusion injury. Cardiovasc Diabetol. 2020 Jun 15;19(1):91. doi: 10.1186/s12933-020-01066-9
   PubMed Web of Science ®Google Scholar
• 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 Mar;104:298–310. doi: 10.1016/j.freeradbiomed.2017.01.035
   PubMed Web of Science ®Google Scholar
• Zinman B, Inzucchi SE, Lachin JM, et al. Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOME™). Cardiovasc Diabetol. 2014 Jun 19;13(1):102. doi: 10.1186/1475-2840-13-102
   PubMedGoogle Scholar
• Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015 Nov 26;373(22):2117–2128. doi: 10.1056/NEJMoa1504720
   PubMed Web of Science ®Google Scholar
• Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019 Jan 24;380(4):347–357. doi: 10.1056/NEJMoa1812389
   PubMed Web of Science ®Google Scholar
• Bhatt DL, Szarek M, Steg PG, et al. Sotagliflozin in patients with diabetes and recent worsening Heart failure. N Engl J Med. 2020;384(2):117–128. doi: 10.1056/NEJMoa2030183
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in Heart failure. NEJM. 2020 Oct 8;383(15):1413–1424. doi: 10.1056/NEJMoa2022190
   PubMed Web of Science ®Google Scholar
• Anker SD, Butler J, Filippatos G, et al. Empagliflozin in Heart failure with a Preserved ejection fraction. N Engl J Med. 2021;385(16):1451–1461. doi: 10.1056/NEJMoa2107038
   PubMed Web of Science ®Google Scholar
• Braunwald E, Longo DL. Gliflozins in the management of cardiovascular disease. N Engl J Med. 2022;386(21):2024–2034. doi: 10.1056/NEJMra2115011
   PubMed Web of Science ®Google Scholar
• Murashima M, Tanaka T, Kasugai T, et al. Sodium-glucose cotransporter 2 inhibitors and anemia among diabetes patients in real clinical practice. J Diabetes Investig. 2022 Apr;13(4):638–646. doi: 10.1111/jdi.13717
   PubMed Web of Science ®Google Scholar
• Fernandes GC, Fernandes A, Cardoso R, et al. Association of SGLT2 inhibitors with arrhythmias and sudden cardiac death in patients with type 2 diabetes or heart failure: a meta-analysis of 34 randomized controlled trials. Heart Rhythm. 2021 Jul 01;18(7):1098–1105. doi: 10.1016/j.hrthm.2021.03.028
   PubMed Web of Science ®Google Scholar
• Gao J, Xue G, Zhan G, et al. Benefits of SGLT2 inhibitors in arrhythmias. Front Cardiovasc Med. 2022;9:1011429. doi: 10.3389/fcvm.2022.1011429
   PubMed Web of Science ®Google Scholar
• Kolesnik E, Scherr D, Rohrer U, et al. SGLT2 inhibitors and their antiarrhythmic properties. Int J Mol Sci. 2022 Jan 31;23(3):1678. doi: 10.3390/ijms23031678
   PubMed Web of Science ®Google Scholar
• Huang K, Luo X, Liao B, et al. Insights into SGLT2 inhibitor treatment of diabetic cardiomyopathy: focus on the mechanisms. Cardiovasc Diabetol. 2023 Apr 13;22(1):86. doi: 10.1186/s12933-023-01816-5
   PubMed Web of Science ®Google Scholar
• Thiele K, Rau M, Hartmann NK, et al. Effects of empagliflozin on erythropoiesis in patients with type 2 diabetes: data from a randomized, placebo-controlled study. Diab Obes Metab. 2021 Dec;23(12):2814–2818. doi: 10.1111/dom.14517
   PubMed Web of Science ®Google Scholar
• 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 May;21(5):665–675. doi: 10.1002/ejhf.1432
   PubMed Web of Science ®Google Scholar
• McMurray JJV, DeMets DL, Inzucchi SE, et al. The dapagliflozin and prevention of adverse-outcomes in Heart failure (DAPA-HF) trial: baseline characteristics. Eur J Heart Fail. 2019 Nov;21(11):1402–1411. doi: 10.1002/ejhf.1548
   PubMed Web of Science ®Google Scholar
• Solomon SD, Jhund PS, Claggett BL, et al. Effect of dapagliflozin in patients with HFrEF treated with Sacubitril/Valsartan: the DAPA-HF trial. JACC Heart Fail. 2020 Oct;8(10):811–818. doi: 10.1016/j.jchf.2020.04.008
   PubMed Web of Science ®Google Scholar
• Iacoviello M, Marini M, Gori M, et al. DAPA-HF applicability: the point of view of a cardiology setting. Acta Cardiol. 2023 Aug;22:1–6.
   Google Scholar
• Cannon CP, Pratley R, Dagogo-Jack S, et al. Cardiovascular outcomes with ertugliflozin in type 2 diabetes. N Engl J Med. 2020 Oct 8;383(15):1425–1435. doi: 10.1056/NEJMoa2004967
   PubMed Web of Science ®Google Scholar
• Cannon CP, McGuire DK, Pratley R, et al. Design and baseline characteristics of the eValuation of ERTugliflozin effIcacy and safety CardioVascular outcomes trial (VERTIS-CV). Am Heart J. 2018 Dec;206:11–23.
   PubMed Web of Science ®Google Scholar
• Cosentino F, Cannon CP, Cherney DZI, et al. Efficacy of ertugliflozin on Heart failure-related events in patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease: results of the VERTIS CV trial. Circulation. 2020 Dec 8;142(23):2205–2215. doi: 10.1161/CIRCULATIONAHA.120.050255
   PubMed Web of Science ®Google Scholar
• Packer M, Anker SD, Butler J, et al. Effect of empagliflozin on the clinical stability of patients with Heart failure and a reduced ejection fraction: the EMPEROR-Reduced trial. Circulation. 2021 Jan 26;143(4):326–336. doi: 10.1161/CIRCULATIONAHA.120.051783
   PubMed Web of Science ®Google Scholar
• Packer M, Butler J, Filippatos GS, et al. Evaluation of the effect of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality of patients with chronic heart failure and a reduced ejection fraction: rationale for and design of the EMPEROR-Reduced trial. Eur J Heart Fail. 2019 Oct;21(10):1270–1278. doi: 10.1002/ejhf.1536
   PubMed Web of Science ®Google Scholar
• Packer M, Anker SD, Butler J, et al. Empagliflozin in patients with Heart failure, reduced ejection fraction, and volume overload: EMPEROR-Reduced trial. J Am Coll Cardiol. 2021 Mar 23;77(11):1381–1392. doi: 10.1016/j.jacc.2021.01.033
   PubMed Web of Science ®Google Scholar
• Tager T, Atar D, Agewall S, et al. Comparative efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) for cardiovascular outcomes in type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials. Heart Fail Rev. 2021 Nov;26(6):1421–1435. doi: 10.1007/s10741-020-09954-8
   PubMed Web of Science ®Google Scholar
• Tromp J, Ouwerkerk W, van Veldhuisen DJ, et al. A systematic review and network meta-analysis of pharmacological treatment of Heart failure with reduced ejection fraction. JACC Heart Fail. 2022 Feb;10(2):73–84. doi: 10.1016/j.jchf.2021.09.004
   PubMed Web of Science ®Google Scholar
• Zelniker TA, Wiviott SD, 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 Jan 5;393(10166):31–39. doi: 10.1016/S0140-6736(18)32590-X
   PubMed Web of Science ®Google Scholar
• Requena-Ibanez JA, Santos-Gallego CG, Rodriguez-Cordero A, et al. Mechanistic insights of empagliflozin in nondiabetic patients with HFrEF: from the EMPA-TROPISM study. JACC Heart Fail. 2021 Aug;9(8):578–589. doi: 10.1016/j.jchf.2021.04.014
   PubMed Web of Science ®Google Scholar
• Anker SD, Butler J, Filippatos G, et al. Effect of empagliflozin on cardiovascular and renal outcomes in patients with Heart failure by baseline diabetes status: results from the EMPEROR-Reduced trial. Circulation. 2021 Jan 26;143(4):337–349. doi: 10.1161/CIRCULATIONAHA.120.051824
   PubMed Web of Science ®Google Scholar
• Solomon SD, McMurray JJV, Anand IS, et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med. 2019 Oct 24;381(17):1609–1620. doi: 10.1056/NEJMoa1908655
   PubMed Web of Science ®Google Scholar
• McDonagh TA, Metra M, Adamo M, et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599–3726. doi: 10.1093/eurheartj/ehab368
   PubMed Web of Science ®Google Scholar
• Pfeffer MA, Swedberg K, Granger CB, et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003 Sep 6;362(9386):759–766. doi: 10.1016/S0140-6736(03)14282-1
   PubMed Web of Science ®Google Scholar
• Heidenreich PA, Bozkurt B, Aguilar D, et al. AHA/ACC/HFSA guideline for the management of Heart failure: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e876–e894.
   PubMed Web of Science ®Google Scholar
• Upadhya B, Kitzman DW. Heart failure with preserved ejection fraction: new approaches to diagnosis and management. Clin Cardiol. 2020 Feb;43(2):145–155. doi: 10.1002/clc.23321
   PubMed Web of Science ®Google Scholar
• Anker SD, Butler J, Filippatos G, et al. Baseline characteristics of patients with heart failure with preserved ejection fraction in the EMPEROR-Preserved trial. Eur J Heart Fail. 2020 Dec;22(12):2383–2392. doi: 10.1002/ejhf.2064
   PubMed Web of Science ®Google Scholar
• Anker SD, Butler J, Filippatos GS, et al. Evaluation of the effects of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality in patients with chronic heart failure and a preserved ejection fraction: rationale for and design of the EMPEROR-Preserved trial. Eur J Heart Fail. 2019 Oct;21(10):1279–1287. doi: 10.1002/ejhf.1596
   PubMed Web of Science ®Google Scholar
• Butler J, Siddiqi TJ, Filippatos G, et al. Early benefit with empagliflozin in heart failure with preserved ejection fraction: insights from the EMPEROR-Preserved trial. Eur J Heart Fail. 2022 Feb;24(2):245–248. doi: 10.1002/ejhf.2420
   PubMed Web of Science ®Google Scholar
• Sandhu AT, Cohen DJ. Cost-effectiveness of Sodium-glucose cotransporter-2 inhibitors for patients with Heart failure and Preserved ejection fraction-living on the edge. JAMA Cardiol. 2023 May 1;8(5):415–416.
   PubMed Web of Science ®Google Scholar
• Kittleson MM, Panjrath GS, Amancherla K, et al. ACC Expert consensus decision pathway on management of Heart failure with Preserved ejection fraction: a report of the American College of cardiology solution set oversight committee. J Am Coll Cardiol. 2023 May 9;81(18):1835–1878. doi: 10.1016/j.jacc.2023.03.393
   PubMed Web of Science ®Google Scholar
• Requena-Ibanez JA, Santos-Gallego CG, Rodriguez-Cordero A, et al. Empagliflozin improves quality of life in nondiabetic HFrEF patients. Sub-analysis of the EMPATROPISM trial. Diabetes Metab Syndr. 2022 Feb;16(2):102417. doi: 10.1016/j.dsx.2022.102417
   PubMed Web of Science ®Google Scholar
• Butler J, Filippatos G, Jamal Siddiqi T, et al. Empagliflozin, health status, and quality of life in patients with Heart failure and Preserved ejection fraction: the EMPEROR-Preserved trial. Circulation. 2022 Jan 18;145(3):184–193. doi: 10.1161/CIRCULATIONAHA.121.057812
   PubMed Web of Science ®Google Scholar
• Paolisso P, Bergamaschi L, Gragnano F, et al. Outcomes in diabetic patients treated with SGLT2-inhibitors with acute myocardial infarction undergoing PCI: the SGLT2-I AMI PROTECT registry. Pharmacol Res. 2023 Jan;187:106597.
   PubMed Web of Science ®Google Scholar
• Mone P, Lombardi A, Gambardella J, et al. Empagliflozin improves cognitive impairment in frail older adults with type 2 diabetes and Heart failure with Preserved ejection fraction. Diabetes Care. 2022 May 1;45(5):1247–1251. doi: 10.2337/dc21-2434
   PubMed Web of Science ®Google Scholar
• Unal I, Cansiz D, Beler M, et al. Sodium-dependent glucose co-transporter-2 inhibitor empagliflozin exerts neuroprotective effects in rotenone-induced Parkinson’s disease model in Zebrafish; mechanism involving ketogenesis and autophagy. Brain Res Aug 15:148536. 2023;1820:148536. doi: 10.1016/j.brainres.2023.148536
   PubMed Web of Science ®Google Scholar
• Mone P, Lombardi A, Kansakar U, et al. Empagliflozin improves the MicroRNA signature of endothelial dysfunction in patients with Heart failure with Preserved ejection fraction and diabetes. J Pharmacol Exp Ther. 2023 Jan;384(1):116–122. doi: 10.1124/jpet.121.001251
   PubMed Web of Science ®Google Scholar
• Santos-Gallego CG, Vargas-Delgado AP, Requena-Ibanez JA, et al. Randomized trial of empagliflozin in nondiabetic patients with Heart failure and reduced ejection fraction. J Am Coll Cardiol. 2021 Jan 26;77(3):243–255. doi: 10.1016/j.jacc.2020.11.008
   PubMed Web of Science ®Google Scholar
• Bechmann LE, Emanuelsson F, Nordestgaard BG, et al. SGLT2-inhibition increases total, LDL, and HDL cholesterol and lowers triglycerides: meta-analyses of 60 randomized trials, overall and by dose, ethnicity, and drug type. Atherosclerosis. 2023 Aug;9:117236.
   Google Scholar
• Tanajak P, Sa-Nguanmoo P, Sivasinprasasn S, et al. Cardioprotection of dapagliflozin and vildagliptin in rats with cardiac ischemia-reperfusion injury. J Endocrinol. 2018 Feb;236(2):69–84. doi: 10.1530/JOE-17-0457
   PubMed Web of Science ®Google Scholar
• Hu Z, Ju F, Du L, et al. Empagliflozin protects the heart against ischemia/reperfusion-induced sudden cardiac death. Cardiovasc Diabetol. 2021 Oct 4;20(1):199. doi: 10.1186/s12933-021-01392-6
   PubMed Web of Science ®Google Scholar
• Sayour AA, Celeng C, Olah A, et al. Sodium-glucose cotransporter 2 inhibitors reduce myocardial infarct size in preclinical animal models of myocardial ischaemia-reperfusion injury: a meta-analysis. Diabetologia. 2021 Apr;64(4):737–748. doi: 10.1007/s00125-020-05359-2
   PubMed Web of Science ®Google Scholar
• Schulze PC, Bogoviku J, Westphal J, et al. Effects of early empagliflozin initiation on diuresis and kidney function in patients with acute decompensated Heart failure (EMPAG-HF). Circulation. 2022 Jul 26;146(4):289–298. doi: 10.1161/CIRCULATIONAHA.122.059038
   PubMed Web of Science ®Google Scholar
• Damman K, Beusekamp JC, Boorsma EM, et al. Randomized, double-blind, placebo-controlled, multicentre pilot study on the effects of empagliflozin on clinical outcomes in patients with acute decompensated heart failure (EMPA-RESPONSE-AHF). Eur J Heart Fail. 2020 Apr;22(4):713–722. doi: 10.1002/ejhf.1713
   PubMed Web of Science ®Google Scholar
• Voors AA, Angermann CE, Teerlink JR, et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med. 2022 Mar;28(3):568–574. doi: 10.1038/s41591-021-01659-1.
   PubMed Web of Science ®Google Scholar
• Biegus J, Voors AA, Collins SP, et al. Impact of empagliflozin on decongestion in acute heart failure: the EMPULSE trial. Eur Heart J. 2023 Jan 1;44(1):41–50. doi: 10.1093/eurheartj/ehac530
   PubMed Web of Science ®Google Scholar
• Tromp J, Ponikowski P, Salsali A, et al. Sodium-glucose co-transporter 2 inhibition in patients hospitalized for acute decompensated heart failure: rationale for and design of the EMPULSE trial. Eur J Heart Fail. 2021 May;23(5):826–834. doi: 10.1002/ejhf.2137
   PubMed Web of Science ®Google Scholar
• Kosiborod MN, Angermann CE, Collins SP, et al. Effects of empagliflozin on symptoms, physical limitations, and quality of life in patients hospitalized for acute Heart failure: results from the EMPULSE trial. Circulation. 2022 Jul 26;146(4):279–288. doi: 10.1161/CIRCULATIONAHA.122.059725
   PubMed Web of Science ®Google Scholar
• Cesaro A, Gragnano F, Paolisso P, et al. In-hospital arrhythmic burden reduction in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: insights from the SGLT2-I AMI PROTECT study. Front Cardiovasc Med. 2022;9:1012220. doi: 10.3389/fcvm.2022.1012220
   PubMedGoogle Scholar
• Paolisso P, Bergamaschi L, Cesaro A, et al. Impact of SGLT2-inhibitors on contrast-induced acute kidney injury in diabetic patients with acute myocardial infarction with and without chronic kidney disease: insight from SGLT2-I AMI PROTECT registry. Diabet Res Clin Pract. 2023 Aug;202:110766.
   PubMed Web of Science ®Google Scholar
• Paolisso P, Bergamaschi L, Santulli G, et al. Infarct size, inflammatory burden, and admission hyperglycemia in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: a multicenter international registry. Cardiovasc Diabetol. 2022 May 15;21(1):77. doi: 10.1186/s12933-022-01506-8
   PubMed Web of Science ®Google Scholar
• von Lewinski D, Kolesnik E, Tripolt NJ, et al. Empagliflozin in acute myocardial infarction: the EMMY trial. Eur Heart J. 2022 Nov 1;43(41):4421–4432. doi: 10.1093/eurheartj/ehac494
   PubMed Web of Science ®Google Scholar
• Andelova K, Bacova BS, Sykora M, et al. Mechanisms underlying antiarrhythmic properties of cardioprotective agents impacting inflammation and oxidative stress. Int J Mol Sci. 2022 Jan 26;23(3):1416. doi: 10.3390/ijms23031416
   PubMed Web of Science ®Google Scholar
• Bossi AC, Forloni F, Colombelli PL. A response to: sodium-glucose cotransporter 2 inhibitors and major COVID-19 outcomes: promising mechanisms, conflicting data, and intriguing clinical decisions. Diabetes Ther. 2020 Dec;11(12):3007–3009. doi: 10.1007/s13300-020-00943-6
   PubMed Web of Science ®Google Scholar
• Shimizu W, Kubota Y, Hoshika Y, et al. Effects of empagliflozin versus placebo on cardiac sympathetic activity in acute myocardial infarction patients with type 2 diabetes mellitus: the EMBODY trial. Cardiovasc Diabetol. 2020 Sep 25;19(1):148. doi: 10.1186/s12933-020-01127-z
   PubMed Web of Science ®Google Scholar
• Curtain JP, Docherty KF, Jhund PS, et al. Effect of dapagliflozin on ventricular arrhythmias, resuscitated cardiac arrest, or sudden death in DAPA-HF. Eur Heart J. 2021 Sep 21;42(36):3727–3738. doi: 10.1093/eurheartj/ehab560
   PubMed Web of Science ®Google Scholar
• Olsson LG, Swedberg K, Ducharme A, et al. Atrial fibrillation and risk of clinical events in chronic heart failure with and without left ventricular systolic dysfunction: results from the candesartan in Heart failure-assessment of reduction in mortality and morbidity (CHARM) program. J Am Coll Cardiol. 2006 May 16;47(10):1997–2004. doi: 10.1016/j.jacc.2006.01.060
   PubMed Web of Science ®Google Scholar
• Benjamin EJ, Levy D, Vaziri SM, et al. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart study. JAMA. 1994 Mar 16;271(11):840–844. doi: 10.1001/jama.1994.03510350050036
   PubMed Web of Science ®Google Scholar
• Sato T, Aizawa Y, Yuasa S, et al. The effect of dapagliflozin treatment on epicardial adipose tissue volume. Cardiovasc Diabetol. 2018 Jan 4;17(1):6. doi: 10.1186/s12933-017-0658-8
   PubMedGoogle Scholar
• Thanassoulis G, Massaro JM, O’Donnell CJ, et al. Pericardial fat is associated with prevalent atrial fibrillation: the Framingham Heart study. Circ Arrhythm Electrophysiol. 2010 Aug;3(4):345–350. doi: 10.1161/CIRCEP.109.912055
   PubMed Web of Science ®Google Scholar
• Zelniker TA, Bonaca MP, Furtado RHM, et al. Effect of dapagliflozin on atrial Fibrillation in patients with type 2 diabetes mellitus: insights from the DECLARE-TIMI 58 trial. Circulation. 2020 Apr 14;141(15):1227–1234. doi: 10.1161/CIRCULATIONAHA.119.044183
   PubMed Web of Science ®Google Scholar
• Pandey AK, Okaj I, Kaur H, et al. Sodium-glucose co-transporter inhibitors and atrial Fibrillation: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2021 Sep 7;10(17):e022222. doi: 10.1161/JAHA.121.022222
   PubMed Web of Science ®Google Scholar
• Granger CB, Mahaffey KW. Preventing atrial Fibrillation with treatments for diabetes mellitus. Circulation. 2020 Apr 14;141(15):1235–1237.
   PubMed Web of Science ®Google Scholar
• Packer M, Wilcox CS, Testani JM. Critical analysis of the effects of SGLT2 inhibitors on renal Tubular Sodium, water and chloride homeostasis and their role in influencing Heart failure outcomes. Circulation. 2023 Jul 25;148(4):354–372.
   PubMed Web of Science ®Google Scholar
• Yau K, Dharia A, Alrowiyti I, et al. Prescribing SGLT2 inhibitors in patients with CKD: expanding indications and practical considerations. Kidney Int Rep. 2022 Jul;7(7):1463–1476. doi: 10.1016/j.ekir.2022.04.094
   PubMed Web of Science ®Google Scholar
• Packer M. Mechanisms leading to differential hypoxia-inducible factor signaling in the diabetic kidney: modulation by sglt2 inhibitors and hypoxia mimetics. Am J Kidney Diseases. 2021 Feb 1;77(2):280–286.
   PubMed Web of Science ®Google Scholar
• Onishi A, Fu Y, Darshi M, et al. Effect of renal tubule-specific knockdown of the Na+/H+ exchanger NHE3 in akita diabetic mice. Am J Physiol Renal Physiol. 2019;317(2):F419–F434. doi: 10.1152/ajprenal.00497.2018
   PubMed Web of Science ®Google Scholar
• Kwon O, Myong JP, Lee Y, et al. Sodium-glucose cotransporter-2 inhibitors after acute myocardial infarction in patients with type 2 diabetes: a population-based investigation. J Am Heart Assoc. 2023 Jul 18;12(14):e027824. doi: 10.1161/JAHA.122.027824
   PubMed Web of Science ®Google Scholar
• ElSayed NA, Aleppo G, Aroda VR, et al. Cardiovascular disease and risk management: standards of Care in diabetes-2023. Diabetes Care. 2023 Jan 1;46(Suppl 1):S158–S190. doi: 10.2337/dc23-S010
   PubMedGoogle Scholar
• Writing C, Maddox TM, Januzzi JL Jr., et al. Update to the 2017 ACC Expert consensus decision pathway for optimization of Heart failure treatment: answers to 10 pivotal issues about Heart failure with reduced ejection fraction: a report of the American college of cardiology solution set oversight committee. J Am Coll Cardiol. 2021 Feb 16;77(6):772–810. doi: 10.1016/j.jacc.2020.11.022
   PubMed Web of Science ®Google Scholar
• Santulli G, Varzideh F, Forzano I, et al. Functional and clinical importance of SGLT2-inhibitors in frailty: from the kidney to the Heart. Hypertension. 2023 Jul 5;80(9):1800–1809. doi: 10.1161/HYPERTENSIONAHA.123.20598
   PubMed Web of Science ®Google Scholar
• Chen S, Wang Q, Christodoulou A, et al. Sodium glucose cotransporter-2 inhibitor empagliflozin reduces infarct size independently of Sodium glucose cotransporter-2. Circulation. 2023 Jan 17;147(3):276–279. doi: 10.1161/CIRCULATIONAHA.122.061688
   PubMedGoogle Scholar
• 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 Mar;60(3):568–573. doi: 10.1007/s00125-016-4134-x
   PubMed Web of Science ®Google Scholar
• Iborra-Egea O, Santiago-Vacas E, Yurista SR, et al. Unraveling the molecular mechanism of action of empagliflozin in Heart failure with reduced ejection fraction with or without diabetes. JACC Basic Transl Sci. 2019 Nov;4(7):831–840. doi: 10.1016/j.jacbts.2019.07.010
   PubMedGoogle Scholar
• Takano M, Kondo H, Harada T, et al. Empagliflozin Suppresses the Differentiation/Maturation of Human Epicardial Preadipocytes and Improves Paracrine Secretome Profile Hemodynamics in patients with type 2 diabetes mellitus. JACC Basic Transl Sci. 2023;8(9):1081–1097. doi: 10.1016/j.jacbts.2023.05.007
   PubMedGoogle Scholar
• Mone P, Varzideh F, Jankauskas SS, et al. SGLT2 inhibition via empagliflozin improves endothelial function and reduces mitochondrial oxidative stress: insights from frail hypertensive and diabetic patients. Hypertension. 2022 Aug;79(8):1633–1643. doi: 10.1161/HYPERTENSIONAHA.122.19586
   PubMed Web of Science ®Google Scholar
• Kolijn D, Pabel S, Tian Y, et al. Empagliflozin improves endothelial and cardiomyocyte function in human heart failure with preserved ejection fraction via reduced pro-inflammatory-oxidative pathways and protein kinase galpha oxidation. Cardiovasc Res. 2021 Jan 21;117(2):495–507. doi: 10.1093/cvr/cvaa123
   PubMed Web of Science ®Google Scholar
• Varzideh F, Kansakar U, Santulli G. SGLT2 inhibitors in cardiovascular medicine. Eur Heart J Cardiovasc Pharmacother. 2021 Jul 23;7(4):e67–e68. doi: 10.1093/ehjcvp/pvab039.
   Google Scholar