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The Use of Sodium-Glucose Cotransporter-2 Inhibitors in Coronary Revascularization: Where Are We Now? A Systematic Review

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Abstract

Introduction

Diabetes and coronary artery disease are two common conditions that often co-exist. In recent years, sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to provide significant cardioprotective benefits, especially among patients with heart failure.

Objective

In this systematic review, we look to identify the outcomes SGLT2i use in patients undergoing coronary revascularization.

Methods

Pubmed and Embase were systematically searched for articles describing the outcomes of patients taking SGLT2i and undergoing coronary revascularization. 834 titles and abstracts were screened, 42 full texts were reviewed, and 18 studies were found to meet the inclusion criteria and were included in this review.

Results

For patients undergoing coronary artery bypass grafting and percutaneous coronary intervention, the use of SGLT2i resulted in reductions in mortality, hospitalization for heart failure, and improved blood glucose; however, these benefits were not consistently reported in the literature. Reduced inflammatory markers and positive cardiac remodeling were identified among patients taking SGLT2i.

Conclusions

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to provide benefits for patients with heart failure along with a host of positive modulatory effects on the cardiovascular system, including reductions in inflammatory properties, hypertension, and left ventricular volume load. Given the clear benefit provided by SGLT2i to patients with cardiovascular disease and a host of positive properties that are expected to be protective for patients with ischemic heart disease, future investigation into the relationship between SGLT2i and outcomes for patients undergoing revascularization is imperative.

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References

  1. Htay T, Soe K, Lopez-Perez A, Doan AH, Romagosa MA, Aung K. Mortality and cardiovascular disease in type 1 and type 2 diabetes. Curr Cardiol Rep. 2019;21:1–7.

    Article  Google Scholar 

  2. Navaratnarajah M, Rea R, Evans R, Gibson F, Antoniades C, Keiralla A, et al. Effect of glycaemic control on complications following cardiac surgery: literature review. J Cardiothorac Surg. 2018;13:10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Halkos ME, Puskas JD, Lattouf OM, Kilgo P, Kerendi F, Song HK, et al. Elevated preoperative hemoglobin A1c level is predictive of adverse events after coronary artery bypass surgery. J Thorac Cardiovasc Surg. 2008;136:631–40.

    Article  PubMed  Google Scholar 

  4. Henning RJ. Type-2 diabetes mellitus and cardiovascular disease. Future Cardiol. 2018;14:491–509.

    Article  CAS  PubMed  Google Scholar 

  5. Rieg T, Vallon V. Development of SGLT1 and SGLT2 inhibitors. Diabetologia. 2018;61:2079–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Stone JA, Houlden RL, Lin P, Udell JA, Verma S. Cardiovascular protection in people with diabetes. Can J Diabetes. 2018;42:S162–9.

    Article  PubMed  Google Scholar 

  7. Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020;41:255–323.

    Article  PubMed  Google Scholar 

  8. O’Meara E, McDonald M, Chan M, Ducharme A, Ezekowitz JA, Giannetti N, et al. CCS/CHFS heart failure guidelines: clinical trial update on functional mitral regurgitation, SGLT2 Inhibitors, ARNI in HFpEF, and Tafamidis in Amyloidosis. Can J Cardiol. 2020;36:159–69.

    Article  PubMed  Google Scholar 

  9. Thourani VH, Weintraub WS, Stein B, Gebhart SSP, Craver JM, Jones EL, et al. Influence of diabetes mellitus on early and late outcome after coronary artery bypass grafting. Ann Thorac Surg. 1999;67:1045.

    Article  CAS  PubMed  Google Scholar 

  10. Carson JL, Scholz PM, Chen AY, Peterson ED, Gold J, Schneider SH. Diabetes mellitus increases short-term mortality and morbidity in patients undergoing coronary artery bypass graft surgery. J Am Coll Cardiol. 2002;40:418–23.

    Article  PubMed  Google Scholar 

  11. Woods SE, Smith JM, Sohail S, Sarah A, Engle A. The influence of type 2 diabetes mellitus in patients undergoing coronary artery bypass graft surgery: an 8-year prospective cohort study. Chest. 2004;126:1789–95.

    Article  PubMed  Google Scholar 

  12. Cardona S, Pasquel FJ, Fayfman M, Peng L, Jacobs S, Vellanki P, et al. Hospitalization costs and clinical outcomes in CABG patients treated with intensive insulin therapy. J Diabetes Complications. 2017;31:742–7.

    Article  PubMed  Google Scholar 

  13. ADVANCE Collaborative Group; Patel A, MacMahon S, Chalmers J, Neal B, Billot L, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Eng J Med 2008;358:2560–72.

  14. Skyler JS, Bergenstal R, Bonow RO, Buse J, Deedwania P, Gale EAM, et al. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA Diabetes Trials. Diabetes Care. 2009;32:187–92.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Turnbull FM, Abraira C, Anderson RJ, Byington RP, Chalmers JP, Duckworth WC, et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia. 2009;52:2288–98.

    Article  CAS  PubMed  Google Scholar 

  16. Liosis S, Hochadel M, Darius H, Behrens S, Mudra H, Lauer B, et al. Effect of renal insufficiency and diabetes mellitus on in-hospital mortality after acute coronary syndromes treated with primary PCI. Results from the ALKK PCI Registry. Int J Cardiol. 2019;292:43–9.

    Article  PubMed  Google Scholar 

  17. Karayiannides S, Norhammar A, Frøbert O, James SK, Lagerqvist B, Lundman P. Prognosis in patients with diabetes mellitus and STEMI undergoing primary PCI. J Am Coll Cardiol. 2018;72:1427–8.

    Article  PubMed  Google Scholar 

  18. Cannon CP, Perkovic V, Agarwal R, Baldassarre J, Bakris G, Charytan DM, et al. Evaluating the effects of canagliflozin on cardiovascular and renal events in patients with type 2 diabetes mellitus and chronic kidney disease according to baseline HbA1c, Including Those With HbA1c <7%: Results From the CREDENCE Trial. Circulation. 2020;141:407–10.

    Article  PubMed  Google Scholar 

  19. Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Eng J Med. 2020;383:1413–24.

    Article  CAS  Google Scholar 

  20. Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Eng J Med. 2021;385:1451–61.

    Article  CAS  Google Scholar 

  21. Ferrannini E, Mark M, Mayoux E. CV Protection in the EMPA-REG OUTCOME Trial: A “Thrifty Substrate” Hypothesis. Diabetes Care. 2016;39:1108–14.

    Article  PubMed  Google Scholar 

  22. Fitchett D, Zinman B, Wanner C, Lachin JM, Hantel S, Salsali A, et al. Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME® trial. Eur Heart J. 2016;37:1526–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Verma S, Mazer CD, Fitchett D, Inzucchi SE, Pfarr E, George JT, et al. Empagliflozin reduces cardiovascular events, mortality and renal events in participants with type 2 diabetes after coronary artery bypass graft surgery: subanalysis of the EMPA-REG OUTCOME® randomised trial. Diabetologia. 2018;61:1712–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Perkovic V, de Zeeuw D, Mahaffey KW, Fulcher G, Erondu N, Shaw W, et al. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. Lancet Diabetes Endocrinol. 2018;6:691–704.

    Article  CAS  PubMed  Google Scholar 

  25. Solomon SD, McMurray JJV, Claggett B, de Boer RA, DeMets D, Hernandez AF, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Eng J Med. 2022;387:1089–98.

    Article  Google Scholar 

  26. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Eng J Med. 2017;377:644–57.

    Article  CAS  Google Scholar 

  27. Olsen MB, Gregersen I, Sandanger Ø, Yang K, Sokolova M, Halvorsen BE, et al. Targeting the inflammasome in cardiovascular disease. JACC Basic Transl Sci. 2022;7:84–98.

    Article  PubMed  Google Scholar 

  28. Paolisso P, Foà A, Bergamaschi L, Donati F, Fabrizio M, Chiti C, et al. Hyperglycemia, inflammatory response and infarct size in obstructive acute myocardial infarction and MINOCA. Cardiovasc Diabetol. 2021;20(1):33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Paolisso P, Bergamaschi L, Santulli G, Gallinoro E, Cesaro A, Gragnano F, 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;21:1–12.

    Article  Google Scholar 

  30. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535–b2535.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700–b2700.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Sardu C, Massetti M, Testa N, di Martino L, Castellano G, Turriziani F, et al. Effects of Sodium-Glucose Transporter 2 Inhibitors (SGLT2-I) in Patients With Ischemic Heart Disease (IHD) Treated by Coronary Artery Bypass Grafting via MiECC: Inflammatory Burden, and Clinical Outcomes at 5 Years of Follow-Up. Front Pharmacol. 2021;12:1–10.

    Article  Google Scholar 

  33. Lee SJ, Lee KH, Oh HG, Seo HJ, Jeong SJ, Kim CH. Effect of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase 4 inhibitors on cardiovascular function in patients with type 2 diabetes mellitus and coronary artery disease. J Obes Metab Syndr. 2019;28:254–61.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Lee H-F, Chan Y-H, Chuang C, Li P-R, Yeh Y-H, Hsiao F-C, et al. Cardiovascular, renal, and lower limb outcomes in patients with type 2 diabetes after percutaneous coronary intervention and treated with sodium–glucose cotransporter 2 inhibitors vs. dipeptidyl peptidase-4 inhibitors. Eur Heart J Cardiovasc Pharmacother. 2023;9:301–10.

    Article  PubMed  Google Scholar 

  35. Paolisso P, Bergamaschi L, Gragnano F, Gallinoro E, Cesaro A, Sardu C, 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;187: 106597.

    Article  CAS  PubMed  Google Scholar 

  36. Lin Y, Zhou F, Wang X, Guo Y, Chen W. Effect of dapagliflozin on clinical outcome after drug-eluting stent implantation in elderly T2DM patients: a real-world study. Comput Math Methods Med. 2023;2023:1–5.

    Article  Google Scholar 

  37. Marfella R, Sardu C, D’Onofrio N, Fumagalli C, Scisciola L, Sasso FC, et al. SGLT-2 inhibitors and in-stent restenosis-related events after acute myocardial infarction: an observational study in patients with type 2 diabetes. BMC Med. 2023;21(1):71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Adel SMH, Jorfi F, Mombeini H, Rashidi H, Fazeli S. Effect of a low dose of empagliflozin on short-term outcomes in type 2 diabetics with acute coronary syndrome after percutaneous coronary intervention. Saudi Med J. 2022;43:458–64.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Feitosa MPM, Lima EG, Abizaid AAC, Mehran R, Lopes NHM, de Assis Fischer Ramos T, et al. The safety of SGLT-2 inhibitors in diabetic patients submitted to elective percutaneous coronary intervention regarding kidney function: SAFE-PCI pilot study. Diabetol Metab Syndr. 2023;15:138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hua R, Ding N, Guo H, Wu Y, Yuan Z, Li T. Contrast-induced acute kidney injury in patients on SGLT2 inhibitors undergoing percutaneous coronary interventions: a propensity-matched analysis. Front Cardiovasc Med. 2022;9:1–9.

    Article  Google Scholar 

  41. Khorlampenko AA, Karetnikova VN, Kochergina AM, Ignatova JS, Dyleva JA, Gruzdeva OL. Effect of empagliflosin on renal filtration in patients with coronary heart disease undergoing percutaneous coronary intervention [in Russian]. Kardiologiya. 2020;60:63–8.

    Article  Google Scholar 

  42. von Lewinski D, Kolesnik E, Tripolt NJ, Pferschy PN, Benedikt M, Wallner M, et al. Empagliflozin in acute myocardial infarction: the EMMY trial. Eur Heart J. 2022;43:4421–32.

    Article  Google Scholar 

  43. Zhu Y, Zhang J, Yan X, Sun L, Ji Y, Wang F. Effect of dapagliflozin on the prognosis of patients with acute myocardial infarction undergoing percutaneous coronary intervention. Cardiovasc Diabetol. 2022;21:1–10.

    Article  CAS  Google Scholar 

  44. Hashikata T, Ikutomi M, Jimba T, Shindo A, Kakuda N, Katsushika S, et al. Empagliflozin attenuates neointimal hyperplasia after drug-eluting-stent implantation in patients with type 2 diabetes. Heart Vessels. 2020;35:1378–89.

    Article  PubMed  Google Scholar 

  45. Dayem KA, Younis O, Zarif B, Attia S, AbdelSalam A. Impact of dapagliflozin on cardiac function following anterior myocardial infarction in non-diabetic patients—DACAMI (a randomized controlled clinical trial). Int J Cardiol. 2023;379:9–14.

    Article  PubMed  Google Scholar 

  46. Sourij C, Aziz F, Tripolt NJ, Siller-Matula J, Pferschy PN, Kolesnik E, et al. Effects of empagliflozin in women and men with acute myocardial infarction—an analysis from the EMMY trial. Hellenic J Cardiol. 2023. https://doi.org/10.1016/j.hjc.2023.05.007.

    Article  PubMed  Google Scholar 

  47. Benedikt M, Mangge H, Aziz F, Curcic P, Pailer S, Herrmann M, et al. Impact of the SGLT2-inhibitor empagliflozin on inflammatory biomarkers after acute myocardial infarction – a post-hoc analysis of the EMMY trial. Cardiovasc Diabetol. 2023;22:166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. McDonald M, Virani S, Chan M, Ducharme A, Ezekowitz JA, Giannetti N, et al. CCS/CHFS heart failure guidelines update: defining a new pharmacologic standard of care for heart failure with reduced ejection fraction. Can J Cardiol. 2021;37:531–46.

    Article  PubMed  Google Scholar 

  49. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, 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:E895-1032.

    PubMed  Google Scholar 

  50. Sardu C, Trotta MC, Sasso FC, Sacra C, Carpinella G, Mauro C, et al. SGLT2-inhibitors effects on the coronary fibrous cap thickness and MACEs in diabetic patients with inducible myocardial ischemia and multi vessels non-obstructive coronary artery stenosis. Cardiovasc Diabetol. 2023;22:80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Gager GM, von Lewinski D, Sourij H, Jilma B, Eyileten C, Filipiak K, et al. Effects of SGLT2 Inhibitors on Ion Homeostasis and Oxidative Stress associated Mechanisms in Heart Failure. Biomed Pharmacother. 2021;143: 112169.

    Article  CAS  PubMed  Google Scholar 

  52. D’Onofrio N, Sardu C, Trotta MC, Scisciola L, Turriziani F, Ferraraccio F, et al. Sodium-glucose co-transporter2 expression and inflammatory activity in diabetic atherosclerotic plaques: effects of sodium-glucose co-transporter2 inhibitor treatment. Mol Metab. 2021;54: 101337.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Salvatore T, Caturano A, Galiero R, di Martino A, Albanese G, Vetrano E, et al. Cardiovascular benefits from gliflozins: effects on endothelial function. Biomedicines. 2021;9:1356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Paolisso P, Bergamaschi L, Cesaro A, Gallinoro E, Gragnano F, Sardu C, 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. Diabetes Res Clin Pract. 2023;202: 110766.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Cardiac Surgery, Department of Surgery, University of Alberta, Mazankowski Alberta Heart Institute, 4-108A Li Ka Shing Health Research Centre, 8602-112 Street, Edmonton, AB, T6G 2E1, Canada

    Ryaan EL-Andari, Nicholas M. Fialka, Jimmy Kang, Sabin J. Bozso, Jayan Nagendran & Jeevan Nagendran

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  1. Ryaan EL-Andari
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  2. Nicholas M. Fialka
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  3. Jimmy Kang
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Correspondence to Jeevan Nagendran.

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Conflicts of interest/Competing interest

Ryaan EL-Andari, Nicholas Fialka, Jimmy Kang, Sabin J Bozso, Jayan Nagendran, and Jeevan Nagendran declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript.

Author Contributions

REA: study design, conceptualization, literature search, data collection, data analysis, data interpretation, generation of figures, writing of the manuscript, approval of the final manuscript. NF: study design, conceptualization, literature search, data interpretation, writing and proofreading the manuscript, approval of the final manuscript. JK: study design, conceptualization, data interpretation, writing and proofreading the manuscript, approval of the final manuscript. SJB: study design, conceptualization, data interpretation, writing and proofreading the manuscript, approval of the final manuscript. Jayan N: study design, conceptualization, data interpretation, writing and proofreading the manuscript, approval of the final manuscript. Jeevan N: study design, conceptualization, data interpretation, writing and proofreading the manuscript, approval of the final manuscript.

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EL-Andari, R., Fialka, N.M., Kang, J. et al. The Use of Sodium-Glucose Cotransporter-2 Inhibitors in Coronary Revascularization: Where Are We Now? A Systematic Review. Am J Cardiovasc Drugs 24, 55–69 (2024). https://doi.org/10.1007/s40256-023-00618-0

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