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Sodium-Glucose Cotransporter 2 Inhibitors in Frail Patients with Heart Failure: Clinical Experience of a Heart Failure Unit

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Abstract

Objective

The objective of this study was to determine the difference in tolerance for sodium glucose cotransporter 2 inhibitors between patients with heart failure classified as frail according to the FRAIL questionnaire, compared to those with heart failure without frailty.

Methods

A prospective cohort study was performed between 2021 and 2022 that included patients with heart failure at a heart failure unit in Bogotá who were being treated with a sodium glucose cotransporter 2 inhibitor. Clinical and laboratory data were collected during an initial visit and 12–48 weeks after that. The FRAIL questionnaire was applied to all participants through a phone call or during the follow-up visit. The primary outcome was the adverse effect rate and as a secondary outcome we compared the estimated glomerular filtration rate change between frail and non-frail patients.

Results

One hundred and twelve patients were included in the final analysis. Frail patients had a more than twice increased risk of having adverse effects (95% confidence interval 1.5–3.9). Age was also a risk factor for the appearance of these.  The estimated glomerular filtration rate decrease was inversely correlated with the age, left ventricular ejection fraction, and renal function before the use of sodium glucose cotransporter 2 inhibitors.

Conclusions

When prescribing in heart failure, it is important to remember that frail patients are more likely to have adverse effects with the use of sodium glucose cotransporter 2 inhibitors, of which the most common are those related to osmotic diuresis. Nonetheless, these do not appear to increase the risk of discontinuation or abandonment of therapy in this population.

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References

  1. Murphy SP, Ibrahim NE, Januzzi JL. Heart failure with reduced ejection fraction: a review. JAMA. 2020;324(5):488–504. https://doi.org/10.1001/JAMA.2020.10262.

    Article  PubMed  Google Scholar 

  2. Savarese G, Lund LH. Global public health burden of heart failure. Card Fail Rev. 2017;3(1):7. https://doi.org/10.15420/CFR.2016:25:2.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Gómez E. Capítulo 2. Introducción, epidemiología de la falla cardiaca e historia de las clínicas de falla cardiaca en Colombia. Rev Colomb Cardiol. 2016;23:6–12. https://doi.org/10.1016/J.RCCAR.2016.01.004.

    Article  Google Scholar 

  4. Arnott C, Li Q, Kang A, et al. Sodium-glucose cotransporter 2 inhibition for the prevention of cardiovascular events in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. J Am Heart Assoc. 2020;9(3):e014908. https://doi.org/10.1161/JAHA.119.014908.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413–24. https://doi.org/10.1056/NEJMOA2022190.

    Article  CAS  PubMed  Google Scholar 

  6. Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451–61. https://doi.org/10.1056/NEJMOA2107038.

    Article  CAS  PubMed  Google Scholar 

  7. 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. https://doi.org/10.1056/NEJMOA1911303.

    Article  CAS  PubMed  Google Scholar 

  8. Stanton RC. Sodium glucose transport 2 (SGLT2) inhibition decreases glomerular hyperfiltration: is there a role for SGLT2 inhibitors in diabetic kidney disease? Circulation. 2014;129(5):542–4. https://doi.org/10.1161/CIRCULATIONAHA.113.007071.

    Article  PubMed  Google Scholar 

  9. Bosch A, Ott C, Jung S, et al. How does empagliflozin improve arterial stiffness in patients with type 2 diabetes mellitus? Sub analysis of a clinical trial. Cardiovasc Diabetol. 2019;18(1):1–12. https://doi.org/10.1186/S12933-019-0839-8.

    Article  Google Scholar 

  10. 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(6):457–64. https://doi.org/10.1016/j.diabet.2018.09.005.

    Article  CAS  PubMed  Google Scholar 

  11. 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. https://doi.org/10.1007/s00125-017-4509-7.

    Article  CAS  PubMed  Google Scholar 

  12. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failureDeveloped by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2021. doi: https://doi.org/10.1093/EURHEARTJ/EHAB368.

  13. Heidenreich PA, Bozkurt B, Aguilar D, 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. https://doi.org/10.1161/CIR.0000000000001063.

    Article  PubMed  PubMed Central  Google Scholar 

  14. McGovern AP, Dutta N, Munro N, Watters K, Feher M. Dapagliflozin: clinical practice compared with pre-registration trial data. Br J Diabetes. 2014;14(4):138–43. https://doi.org/10.15277/BJDVD.2014.047.

    Article  Google Scholar 

  15. Khan H, Kalogeropoulos AP, Georgiopoulou VV, et al. Frailty and risk for heart failure in older adults: the health, aging, and body composition study. Am Heart J. 2013;166(5):887–94. https://doi.org/10.1016/J.AHJ.2013.07.032.

    Article  PubMed  Google Scholar 

  16. Denfeld QE, Winters-Stone K, Mudd JO, Gelow JM, Kurdi S, Lee CS. The prevalence of frailty in heart failure: a systematic review and meta-analysis. Int J Cardiol. 2017;236:283–9. https://doi.org/10.1016/J.IJCARD.2017.01.153.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Bielecka-Dabrowa A, Ebner N, Dos Santos MR, Ishida J, Hasenfuss G, von Haehling S. Cachexia, muscle wasting, and frailty in cardiovascular disease. Eur J Heart Fail. 2020;22(12):2314–26. https://doi.org/10.1002/EJHF.2011.

    Article  PubMed  Google Scholar 

  18. Vitale C, Jankowska E, Hill L, et al. Heart Failure Association of the European Society of Cardiology position paper on frailty in patients with heart failure. Eur J Heart Fail. 2019;21(11):1299–305. https://doi.org/10.1002/EJHF.1611.

    Article  PubMed  Google Scholar 

  19. Nozaki K, Kamiya K, Hamazaki N, et al. Validity and utility of the questionnaire-based FRAIL scale in older patients with heart failure: findings from the FRAGILE-HF. J Am Med Dir Assoc. 2021;22(8):1621-6.e2. https://doi.org/10.1016/J.JAMDA.2021.02.025.

    Article  PubMed  Google Scholar 

  20. Vuyk J. Pharmacodynamics in the elderly. Best Pract Res Clin Anaesthesiol. 2003;17(2):207–18. https://doi.org/10.1016/S1521-6896(03)00008-9.

    Article  CAS  PubMed  Google Scholar 

  21. Hilmer SN, Gnjidic D. Prescribing for frail older people. Aust Prescr. 2017;40(5):174. https://doi.org/10.18773/AUSTPRESCR.2017.055.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Landi F, Russo A, Liperoti R, et al. Impact of inappropriate drug use on physical performance among a frail elderly population living in the community. Eur J Clin Pharmacol. 2007;63(8):791–9. https://doi.org/10.1007/S00228-007-0321-5.

    Article  CAS  PubMed  Google Scholar 

  23. Peeters LEJ, Kester MP, Feyz L, et al. Pharmacokinetic and pharmacodynamic considerations in the treatment of the elderly patient with hypertension. Expert Opin Drug Metab Toxicol. 2019;15(4):287–97. https://doi.org/10.1080/17425255.2019.1588249.

    Article  CAS  PubMed  Google Scholar 

  24. Rodríguez-Monguió R, Otero MJ, Rovira J. Assessing the economic impact of adverse drug effects. Pharmacoeconomics. 2003;21(9):623–50. https://doi.org/10.2165/00019053-200321090-00002.

    Article  PubMed  Google Scholar 

  25. Lopez D, Murray K, Preen DB, et al. The Hospital Frailty Risk Score identifies fewer cases of frailty in a community-based cohort of older men than the FRAIL Scale and Frailty Index. J Am Med Dir Assoc. 2022;23(8):1348-53.e8. https://doi.org/10.1016/j.jamda.2021.09.033.

    Article  PubMed  Google Scholar 

  26. Butt JH, Dewan P, Merkely E, et al. Efficacy and safety of dapagliflozin according to frailty in heart failure with reduced ejection fraction. Ann Intern Med. 2022. https://doi.org/10.7326/M21-4776.

    Article  PubMed  Google Scholar 

  27. Alvarado BE, Zunzunegui MV, Béland F, Bamvita JM. Life course social and health conditions linked to frailty in Latin American older men and women. J Gerontol A Biol Sci Med Sci. 2008;63(12):1399–406. https://doi.org/10.1093/GERONA/63.12.1399.

    Article  PubMed  Google Scholar 

  28. Dewan P, Jackson A, Jhund PS, et al. The prevalence and importance of frailty in heart failure with reduced ejection fraction: an analysis of PARADIGM-HF and ATMOSPHERE. Eur J Heart Fail. 2020;22(11):2123–33. https://doi.org/10.1002/EJHF.1832.

    Article  PubMed  Google Scholar 

  29. Sanders NA, Supiano MA, Lewis EF, et al. The frailty syndrome and outcomes in the TOPCAT trial. Eur J Heart Fail. 2018;20(11):1570–7. https://doi.org/10.1002/EJHF.1308.

    Article  CAS  PubMed  Google Scholar 

  30. Uchmanowicz I, Wleklik M, Gobbens RJJ. Frailty syndrome and self-care ability in elderly patients with heart failure. Clin Interv Aging. 2015;10:871–7. https://doi.org/10.2147/CIA.S83414.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Nakagaito M, Imamura T, Joho S, Ushijima R, Nakamura M, Kinugawa K. Efficacy of continuing sglt2 inhibitors on outcomes in patients with acute decompensated heart failure. Int Heart J. 2021;62(4):885–90. https://doi.org/10.1536/ihj.21-022.

    Article  PubMed  Google Scholar 

  32. Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436–46. https://doi.org/10.1056/NEJMOA2024816/SUPPL_FILE/NEJMOA2024816_DATA-SHARING.PDF.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the Department of Cardiology of Hospital Universitario Fundación Santa Fe de Bogotá and the Faculty of Medicine of Universidad de los Andes, Bogotá, Colombia.

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Authors and Affiliations

  1. School of Medicine, Universidad de los Andes, Cra. 7 #116-5, 110121, Bogotá, Colombia

    Daniel Villarreal

  2. Heart Failure Unit, Internal Medicine Department, University Hospital Fundación Santa Fe de Bogotá, Bogotá, Colombia

    Hernán Ramírez

  3. School of Medicine, Universidad de los Andes, Bogotá, Colombia

    Valentina Sierra & Juan S. Amarís

  4. Geriatrics Team and Palliative Care Unit, Internal Medicine Department, University Hospital Fundación Santa Fe de Bogotá, Bogotá, Colombia

    Ana M. Lopez-Salazar

  5. Heart Failure Unit, Internal Medicine Department, University Hospital Fundación Santa Fe de Bogotá, Bogotá, Colombia

    Gina González-Robledo

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  1. Daniel Villarreal
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Corresponding author

Correspondence to Daniel Villarreal.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not for-profit sectors.

Conflicts of Interest/Competing Interests

Daniel Villarreal, Hernán Ramírez, Valentina Sierra, Juan S. Amarís, Ana M. Lopez-Salazar, and Gina González-Robledo have no financial or non-financial conflicts of interest that are directly relevant to the content of this article.

Ethics Approval

The investigation conforms with the principles outlined in the Declaration of Helsinki and local and international guidelines on ethical research and was approved by the Ethics Committee of University Hospital Fundación Santa Fe de Bogotá before data collection was started.

Consent to Participate

Consent was obtained from each of the participants prior to their enrollment in the study.

Consent for Publication

Not applicable.

Availability of Data and Material

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code Availability

Not applicable.

Authors’ Contributions

All the authors contributed in the conceptualization, data analysis, writing, reviewing, and editing of the article. DV, VS, and JA performed the data recollection and curation. DV was the author in charge of project resource administration.

Supplementary Information

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Supplementary file1 (PDF 231 kb)

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Villarreal, D., Ramírez, H., Sierra, V. et al. Sodium-Glucose Cotransporter 2 Inhibitors in Frail Patients with Heart Failure: Clinical Experience of a Heart Failure Unit. Drugs Aging 40, 293–299 (2023). https://doi.org/10.1007/s40266-022-01004-2

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