The use of SGLT2 inhibitors and their impact on coronary artery disease: A literature review
DOI:
https://doi.org/10.33448/rsd-v12i9.41542Keywords:
Acute Coronary Syndrome; Hypoglycemics; Coronary disease; Cardiopathies.Abstract
Introduction: Acute Coronary Syndrome is responsible for more than one million hospital admissions per year. People with Type 2 Diabetes Mellitus have an increased risk factor for developing this syndrome. Sodium glucose type 2 co-transporter (SGLT2) inhibitors, a medication initially developed as a hypoglycemic agent, have shown favorable responses to protect against cardiovascular events in this population. Objective: This review seeks to assess the benefit of using SGLT2 inhibitors in patients with coronary artery disease and its relationship with clinical outcomes (mortality and length of stay). Method: This is a narrative review of the literature, with data collection in the bases: Scielo, and MEDLINE. Complete articles were included, in English, Portuguese and Spanish, published from 2005 onwards. Duplicate works, with straying from the objective, incomplete and in other languages were excluded. A total of 51 studies composed this review. Results and Discussion: SGLT2 inhibitors are a class of hypoglycemic agents that reduce glucose reabsorption in the proximal renal tubes, increasing urinary glucose excretion through an insulin-independent mechanism. These drugs are known to alleviate oxidative stress and endothelial dysfunction, downregulate systemic inflammation and sympathetic activity, stimulate erythropoietin production, improve heart energy, and reduce preload, afterload, and ventricular mass. Although their impact on atherosclerotic outcomes in large studies of cardiovascular outcomes has been minimal, these properties should, in theory, be beneficial for patients with acute coronary syndrome. Conclusion: SGLT2 inhibitors seem promising in the treatment of acute coronary syndrome, and may be able to improve survival and outcomes in this population.
References
American Diabetes Association (2018). 9. cardiovascular disease and Risk Management: Standards of Medical Care in Diabetes-2018. Diabetes care, 41(Suppl 1), S86–S104. https://doi.org/10.2337/dc18-S009
André, R., Bongard, V., Elosua, R., Kirchberger, I., Farmakis, D., Häkkinen, U., Fusco, D., Torre, M., Garel, P., Araújo, C., Meisinger, C., Lekakis, J., Malmivaara, A., Dovali, M., Pereira, M., Marrugat, J., & Ferrières, J. (2014). International differences in acute coronary syndrome patients' baseline characteristics, clinical management and outcomes in Western Europe: the EURHOBOP study. Heart (British Cardiac Society), 100(15), 1201–1207. https://doi.org/10.1136/heartjnl-2013-305196
Aronson, D., Musallam, A., Lessick, J., Dabbah, S., Carasso, S., Hammerman, H., Reisner, S., Agmon, Y., & Mutlak, D. (2010). Impact of diastolic dysfunction on the development of heart failure in diabetic patients after acute myocardial infarction. Circulation. Heart failure, 3(1), 125–131. https://doi.org/10.1161/CIRCHEARTFAILURE.109.877340
AstraZeneca. (2023). Dapaglifozin Effects on Cardiovascular Events in Patients With an Acute Heart Attack (DAPA-MI). https://clinicaltrials.gov/ct2/show/NCT04564742
Bancks, M. P., Ning, H., Allen, N. B., Bertoni, A. G., Carnethon, M. R., Correa, A., Echouffo-Tcheugui, J. B., Lange, L. A., Lloyd-Jones, D. M., & Wilkins, J. T. (2019). Long-term Absolute Risk for Cardiovascular Disease Stratified by Fasting Glucose Level. Diabetes care, 42(3), 457–465. https://doi.org/10.2337/dc18-1773
Bami, K., Gandhi, S., Leong-Poi, H., Yan, A. T., Ho, E., Zahrani, M., Garg, V., Zuo, F., Teoh, H., Quan, A., Leiter, L. A., Gilbert, R. E., Zinman, B., Thorpe, K. E., Jüni, P., Mazer, C. D., Verma, S., Ong, G., & Connelly, K. A. (2020). Effects of Empagliflozin on Left Ventricular Remodeling in Patients with Type 2 Diabetes and Coronary Artery Disease: Echocardiographic Substudy of the EMPA-HEART CardioLink-6 Randomized Clinical Trial. Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography, 33(5), 644–646. https://doi.org/10.1016/j.echo.2020.02.005
Bhatt, A. S., Ambrosy, A. P., & Velazquez, E. J. (2017). Adverse Remodeling and Reverse Remodeling After Myocardial Infarction. Current cardiology reports, 19(8), 71. https://doi.org/10.1007/s11886-017-0876-4
Boehringer Ingelhein. (2023). EMPACT-MI: A Study to Test Whether Empagliflozin Can Lower the Risk of Heart Failure and Death in People Who Had a Heart Attack (Myocardial Infarction). https://clinicaltrials.gov/ct2/show/NCT04509674
Buse, J. B., Wexler, D. J., Tsapas, A., Rossing, P., Mingrone, G., Mathieu, C., D'Alessio, D. A., & Davies, M. J. (2020). 2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes care, 43(2), 487–493. https://doi.org/10.2337/dci19-0066
Chan, G. C., Ng, J. K., Chow, K. M., & Szeto, C. C. (2023). SGLT2 inhibitors reduce adverse kidney and cardiovascular events in patients with advanced diabetic kidney disease: A population-based propensity score-matched cohort study. Diabetes research and clinical practice, 195, 110200. https://doi.org/10.1016/j.diabres.2022.110200
Chen, S., Coronel, R., Hollmann, M. W., Weber, N. C., & Zuurbier, C. J. (2022). Direct cardiac effects of SGLT2 inhibitors. Cardiovascular diabetology, 21(1), 45. https://doi.org/10.1186/s12933-022-01480-1
Cosentino, F., Grant, P. J., Aboyans, V., Bailey, C. J., Ceriello, A., Delgado, V., Federici, M., Filippatos, G., Grobbee, D. E., Hansen, T. B., Huikuri, H. V., Johansson, I., Jüni, P., Lettino, M., Marx, N., Mellbin, L. G., Östgren, C. J., Rocca, B., Roffi, M., Sattar, N., & ESC Scientific Document Group (2020). 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. European heart journal, 41(2), 255–323. https://doi.org/10.1093/eurheartj/ehz486
Davies, M. J., D'Alessio, D. A., Fradkin, J., Kernan, W. N., Mathieu, C., Mingrone, G., Rossing, P., Tsapas, A., Wexler, D. J., & Buse, J. B. (2018). Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes care, 41(12), 2669–2701. https://doi.org/10.2337/dci18-0033
Elrakaybi, A., Laubner, K., Zhou, Q., Hug, M. J., & Seufert, J. (2022). Cardiovascular protection by SGLT2 inhibitors - Do anti-inflammatory mechanisms play a role?. Molecular metabolism, 64, 101549. https://doi.org/10.1016/j.molmet.2022.101549
From, A. M., Scott, C. G., & Chen, H. H. (2010). The development of heart failure in patients with diabetes mellitus and pre-clinical diastolic dysfunction a population-based study. Journal of the American College of Cardiology, 55(4), 300–305. https://doi.org/10.1016/j.jacc.2009.12.003
Gach, O., El, H. Z., & Lancellotti, P. (2018). Syndrome coronarien aigu [Acute coronary syndrome]. Revue medicale de Liege, 73(5-6), 243–250.
Go, A. S., Mozaffarian, D., Roger, V. L., Benjamin, E. J., Berry, J. D., Borden, W. B., Bravata, D. M., Dai, S., Ford, E. S., Fox, C. S., Franco, S., Fullerton, H. J., Gillespie, C., Hailpern, S. M., Heit, J. A., Howard, V. J., Huffman, M. D., Kissela, B. M., Kittner, S. J., Lackland, D. T., & American Heart Association Statistics Committee and Stroke Statistics Subcommittee (2013). Heart disease and stroke statistics--2013 update: a report from the American Heart Association. Circulation, 127(1), e6–e245. https://doi.org/10.1161/CIR.0b013e31828124ad
Gupta, A., Wang, Y., Spertus, J. A., Geda, M., Lorenze, N., Nkonde-Price, C., D'Onofrio, G., Lichtman, J. H., & Krumholz, H. M. (2014). Trends in acute myocardial infarction in young patients and differences by sex and race, 2001 to 2010. Journal of the American College of Cardiology, 64(4), 337–345. https://doi.org/10.1016/j.jacc.2014.04.054
Jhund P. S. (2022). SGLT2 Inhibitors and Heart Failure with Preserved Ejection Fraction. Heart failure clinics, 18(4), 579–586. https://doi.org/10.1016/j.hfc.2022.03.010
Karangelis, D., Mazer, C. D., Stakos, D., Tzifa, A., Loggos, S., Verma, S., & Mitropoulos, F. (2021). Cardio-Protective Effects of Sodium-Glucose Co-Transporter 2 Inhibitors: Focus on Heart Failure. Current pharmaceutical design, 27(8), 1051–1060. https://doi.org/10.2174/1381612826666201103122813
Kaze, A. D., Zhuo, M., Kim, S. C., Patorno, E., & Paik, J. M. (2022). Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis. Cardiovascular diabetology, 21(1), 47. https://doi.org/10.1186/s12933-022-01476-x
Koufakis, T., Vas, P., Maltese, G., & Kotsa, K. (2022). Antiatherosclerotic Effects of Sodium-Glucose Cotransporter 2 Inhibitors: An Underrecognized Piece of the Big Puzzle?. The Journal of clinical endocrinology and metabolism, 107(10), e4244–e4245. https://doi.org/10.1210/clinem/dgac116
Koufakis, T., Karangelis, D., Androutsopoulou, V., Mikroulis, D., & Kotsa, K. (2023). Management of Type 2 Diabetes in Acute Coronary Syndromes: Current State and Future Perspectives. Current pharmaceutical design, 10.2174/1381612829666230210161306. Advance online publication. https://doi.org/10.2174/1381612829666230210161306
Lan, N. S. R., Fegan, P. G., Rankin, J. M., Bell, D. A., Watts, G. F., & Yeap, B. B. (2019). Implementing simple algorithms to improve glucose and lipid management in people with diabetes and acute coronary syndrome. Diabetic medicine: a journal of the British Diabetic Association, 36(12), 1643–1651. https://doi.org/10.1111/dme.14095
Lan, N. S. R., Fegan, P. G., Yeap, B. B., & Dwivedi, G. (2020). The effects of sodium-glucose cotransporter 2 inhibitors on left ventricular function: current evidence and future directions. ESC heart failure, 6(5), 927–935. https://doi.org/10.1002/ehf2.12505
Lan, N. S. R., Yeap, B. B., Fegan, P. G., Green, G., Rankin, J. M., & Dwivedi, G. (2021). Empagliflozin and left ventricular diastolic function following an acute coronary syndrome in patients with type 2 diabetes. The international journal of cardiovascular imaging, 37(2), 517–527. https://doi.org/10.1007/s10554-020-02034-w
Lanzoni, G.M.M. & Meirelles, B.H.S. (2011). Leadership of the nurse: an integrative literature review. Revista Latino-Americana de Enfermagem. 19(3) <https://doi.org/10.1590/S0104-11692011000300026>. Epub 07 Mar 2012. ISSN 1518-8345. https://doi.org/10.1590/S0104-11692011000300026.
Liu, Z., Ma, X., Ilyas, I., Zheng, X., Luo, S., Little, P. J., Kamato, D., Sahebkar, A., Wu, W., Weng, J., & Xu, S. (2021). Impact of sodium glucose cotransporter 2 (SGLT2) inhibitors on atherosclerosis: from pharmacology to pre-clinical and clinical therapeutics. Theranostics, 11(9), 4502–4515. https://doi.org/10.7150/thno.54498
Lu, H., Tang, B., Zhou, Y., Xu, C., Bundhun, P. K., Tang, Z., & Bao, H. (2019). Short-Term Versus Long-Term Adverse Cardiovascular Outcomes Post Percutaneous Coronary Intervention in Patients with Insulin-Treated Type 2 Diabetes Mellitus: A Simple Meta-Analysis. Diabetes therapy : research, treatment and education of diabetes and related disorders, 10(4), 1487–1497. https://doi.org/10.1007/s13300-019-0656-9
Matsutani, D., Sakamoto, M., Kayama, Y., Takeda, N., Horiuchi, R., & Utsunomiya, K. (2018). Effect of canagliflozin on left ventricular diastolic function in patients with type 2 diabetes. Cardiovascular diabetology, 17(1), 73. https://doi.org/10.1186/s12933-018-0717-9
McMurray, J. J., Gerstein, H. C., Holman, R. R., & Pfeffer, M. A. (2014). Heart failure: a cardiovascular outcome in diabetes that can no longer be ignored. The lancet. Diabetes & endocrinology, 2(10), 843–851. https://doi.org/10.1016/S2213-8587(14)70031-2
Meta-Analysis Research Group in Echocardiography (MeRGE) AMI Collaborators, Møller, J. E., Whalley, G. A., Dini, F. L., Doughty, R. N., Gamble, G. D., Klein, A. L., Quintana, M., & Yu, C. M. (2008). Independent prognostic importance of a restrictive left ventricular filling pattern after myocardial infarction: an individual patient meta-analysis: Meta-Analysis Research Group in Echocardiography acute myocardial infarction. Circulation, 117(20), 2591–2598. https://doi.org/10.1161/CIRCULATIONAHA.107.738625
Mozawa, K., Kubota, Y., Hoshika, Y., Tara, S., Tokita, Y., Yodogawa, K., Iwasaki, Y. K., Yamamoto, T., Takano, H., Tsukada, Y., Asai, K., Miyamoto, M., Miyauchi, Y., Kodani, E., Maruyama, M., Tanabe, J., & Shimizu, W. (2021). Empagliflozin confers reno-protection in acute myocardial infarction and type 2 diabetes mellitus. ESC heart failure, 8(5), 4161–4173. https://doi.org/10.1002/ehf2.13509
Nagueh, S. F., Smiseth, O. A., Appleton, C. P., Byrd, B. F., 3rd, Dokainish, H., Edvardsen, T., Flachskampf, F. A., Gillebert, T. C., Klein, A. L., Lancellotti, P., Marino, P., Oh, J. K., Popescu, B. A., & Waggoner, A. D. (2016). Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography, 29(4), 277–314. https://doi.org/10.1016/j.echo.2016.01.011
Nassif, M. E., & Kosiborod, M. (2018). Are We Ready to Bell The Cat? A Call for Cardiologists to Embrace Glucose-Lowering Therapies Proven to Improve Cardiovascular Outcomes. Circulation, 138(1), 4–6. https://doi.org/10.1161/CIRCULATIONAHA.117.022680
Neal, B., Perkovic, V., Mahaffey, K. W., de Zeeuw, D., Fulcher, G., Erondu, N., Shaw, W., Law, G., Desai, M., Matthews, D. R., & CANVAS Program Collaborative Group (2017). Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. The New England journal of medicine, 377(7), 644–657. https://doi.org/10.1056/NEJMoa1611925
Nelson, A. J., Peterson, E. D., & Pagidipati, N. J. (2019). Atherosclerotic cardiovascular disease and heart failure: Determinants of risk and outcomes in patients with diabetes. Progress in cardiovascular diseases, 62(4), 306–314. https://doi.org/10.1016/j.pcad.2019.07.001
Nunes, F. M. P., & Silva, A. B. da. (2020). Assistência ao paciente com síndrome coronariana aguda: revisão integrativa. Revista De Ciências Da Saúde Nova Esperança, 18(2), 98–106. Recuperado de http://revistanovaesperanca.com.br/index.php/revistane/article/view/527
Soga, F., Tanaka, H., Tatsumi, K., Mochizuki, Y., Sano, H., Toki, H., Matsumoto, K., Shite, J., Takaoka, H., Doi, T., & Hirata, K. I. (2018). Impact of dapagliflozin on left ventricular diastolic function of patients with type 2 diabetic mellitus with chronic heart failure. Cardiovascular diabetology, 17(1), 132. https://doi.org/10.1186/s12933-018-0775-z
Tanaka, H., Soga, F., Tatsumi, K., Mochizuki, Y., Sano, H., Toki, H., Matsumoto, K., Shite, J., Takaoka, H., Doi, T., & Hirata, K. I. (2020). Positive effect of dapagliflozin on left ventricular longitudinal function for type 2 diabetic mellitus patients with chronic heart failure. Cardiovascular diabetology, 19(1), 6. https://doi.org/10.1186/s12933-019-0985-z
Thygesen, K., Alpert, J. S., Jaffe, A. S., Simoons, M. L., Chaitman, B. R., White, H. D., Joint ESC/ACCF/AHA/WHF Task Force for Universal Definition of Myocardial Infarction, Authors/Task Force Members Chairpersons, Thygesen, K., Alpert, J. S., White, H. D., Biomarker Subcommittee, Jaffe, A. S., Katus, H. A., Apple, F. S., Lindahl, B., Morrow, D. A., ECG Subcommittee, Chaitman, B. R., Clemmensen, P. M., & Wagner, D. R. (2012). Third universal definition of myocardial infarction. Journal of the American College of Cardiology, 60(16), 1581–1598. https://doi.org/10.1016/j.jacc.2012.08.001
Tochiya, M., Makino, H., Tamanaha, T., Matsuo, M., Hishida, A., Koezuka, R., Ohata, Y., Tomit,a T., Son, C., Miyamoto, Y., Yasuda, S. & Hosoda, K. (2020) Effect of tofogliflozin on cardiac and vascular endothelial function in patients with type 2 diabetes and heart diseases: a pilot study. J Diabetes Invest. 11:400–404. https://doi.org/10.1111/jdi.13122
Tsai, P. C., Chuang, W. J., Ko, A. M., Chen, J. S., Chiu, C. H., Chen, C. H., & Yeh, Y. H. (2023). Neutral effects of SGLT2 inhibitors in acute coronary syndromes, peripheral arterial occlusive disease, or ischemic stroke: a meta-analysis of randomized controlled trials. Cardiovascular diabetology, 22(1), 57. https://doi.org/10.1186/s12933-023-01789-5
Wang, Y., Yu, Q., Fan, D., & Cao, F. (2012). Coronary heart disease in type 2 diabetes: mechanisms and comprehensive prevention strategies. Expert review of cardiovascular therapy, 10(8), 1051–1060. https://doi.org/10.1586/erc.12.52
Wiviott, S. D., Raz, I., Bonaca, M. P., Mosenzon, O., Kato, E. T., Cahn, A., Silverman, M. G., Zelniker, T. A., Kuder, J. F., Murphy, S. A., Bhatt, D. L., Leiter, L. A., McGuire, D. K., Wilding, J. P. H., Ruff, C. T., Gause-Nilsson, I. A. M., Fredriksson, M., Johansson, P. A., Langkilde, A. M., Sabatine, M. S., … DECLARE–TIMI 58 Investigators (2019). Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. The New England journal of medicine, 380(4), 347–357. https://doi.org/10.1056/NEJMoa1812389
Verma, S., Garg, A., Yan, A. T., Gupta, A. K., Al-Omran, M., Sabongui, A., Teoh, H., Mazer, C. D., & Connelly, K. A. (2016). Effect of Empagliflozin on Left Ventricular Mass and Diastolic Function in Individuals With Diabetes: An Important Clue to the EMPA-REG OUTCOME Trial? Diabetes care, 39(12), e212–e213. https://doi.org/10.2337/dc16-1312
Verma, S., Mazer, C. D., Yan, A. T., Mason, T., Garg, V., Teoh, H., Zuo, F., Quan, A., Farkouh, M. E., Fitchett, D. H., Goodman, S. G., Goldenberg, R. M., Al-Omran, M., Gilbert, R. E., Bhatt, D. L., Leiter, L. A., Jüni, P., Zinman, B., & Connelly, K. A. (2019). Effect of Empagliflozin on Left Ventricular Mass in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease: The EMPA-HEART CardioLink-6 Randomized Clinical Trial. Circulation, 140(21), 1693–1702. https://doi.org/10.1161/CIRCULATIONAHA.119.042375
von Lewinski, D., Kolesnik, E., Tripolt, N. J., Pferschy, P. N., Benedikt, M., Wallner, M., Alber, H., Berger, R., Lichtenauer, M., Saely, C. H., Moertl, D., Auersperg, P., Reiter, C., Rieder, T., Siller-Matula, J. M., Gager, G. M., Hasun, M., Weidinger, F., Pieber, T. R., Zechner, P. M., & Sourij, H. (2022). Empagliflozin in acute myocardial infarction: the EMMY trial. European heart journal, 43(41), 4421–4432. https://doi.org/10.1093/eurheartj/ehac494
Voors, A. A., Angermann, C. E., Teerlink, J. R., Collins, S. P., Kosiborod, M., Biegus, J., Ferreira, J. P., Nassif, M. E., Psotka, M. A., Tromp, J., Borleffs, C. J. W., Ma, C., Comin-Colet, J., Fu, M., Janssens, S. P., Kiss, R. G., Mentz, R. J., Sakata, Y., Schirmer, H., Schou, M., & Ponikowski, P. (2022). The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nature medicine, 28(3), 568–574. https://doi.org/10.1038/s41591-021-01659-1
Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., Mattheus, M., Devins, T., Johansen, O. E., Woerle, H. J., Broedl, U. C., Inzucchi, S. E., & EMPA-REG OUTCOME Investigators (2015). Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. The New England journal of medicine, 373(22), 2117–2128. https://doi.org/10.1056/NEJMoa1504720
Zinman, B., Lachin, J. M., & Inzucchi, S. E. (2016). Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. The New England journal of medicine, 374(11), 1094. https://doi.org/10.1056/NEJMc1600827
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