Department of Internal Medicine, Instituto Ramón y Cajal de Investigación Sanitaria, University Hospital Ramón y Cajal, University of Alcalá, 28034, Madrid, Spain

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Francesc Formiga

Internal Medicine Department, Hospital Universitari de Bellvitge, 08907, Barcelona, Spain

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Jesús Díez-Manglano

Servicio de Medicina Interna, Hospital Royo Villanova Zaragoza, 50015, Zaragoza, Spain

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José María Cepeda

Servicio de Medicina Interna, Hospital Vega Baja, Orihuela, 03314, Alicante, Spain

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Alvaro González-Franco

Servicio de Medicina Interna, Hospital Universitario Central de Asturias, 33011 Oviedo, Asturias, Spain

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Jesús Casado-Cerrada

Internal Medicine, University Hospital of Getafe, 28905, Madrid, Spain

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Published Online:29 Jun 2023https://doi.org/10.2217/fca-2023-0016

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Abstract

Aim: To estimate the projected effectiveness of dapagliflozin in subjects with heart failure (HF) with reduced ejection fraction in clinical practice in Spain. Materials & methods: This multicenter cohort study included subjects aged 50 years or older consecutively hospitalized for HF in internal medicine departments in Spain. The projected clinical benefits of dapagliflozin were estimated based on results from the DAPA-HF trial. Results: A total of 1595 patients were enrolled, of whom 1199 (75.2%) were eligible for dapagliflozin. Within 1 year after discharge, 21.6% of patients eligible for dapagliflozin were rehospitalized for HF and 20.5% died. Full implementation of dapagliflozin led to an absolute risk reduction of 3.5% for mortality (number needed to treat = 28) and 6.5% (number needed to treat = 15) for HF readmission. Conclusion: Treatment with dapagliflozin in clinical practice may markedly reduce mortality and readmissions for HF.

Plain language summary

Heart failure with reduced ejection fraction is a severe disease with a high risk of hospitalization and mortality. With this condition, the heart muscle cannot pump properly. This means that not enough blood is pumped from the heart, reducing the amount of oxygen to the body. Fortunately, there are treatments that reduce this risk, in patients with heart failure. SGLT2 inhibitors, including dapagliflozin, are among the first therapies given to patients with heart failure. In this study, we investigated the potential benefits of adding dapagliflozin to the treatment of patients admitted to the hospital in Spain for heart failure with reduced ejection fraction. Our data showed that dapagliflozin was able to reduce the risk of further events (e.g., heart attack) in these patients.

Tweetable abstract

The implementation of dapagliflozin may translate into substantial reductions in mortality and heart failure readmissions.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. Roger VL. Epidemiology of heart failure: a contemporary perspective. Circ. Res. 128(10), 1421–1434 (2021).
Medline CASGoogle Scholar
2. Groenewegen A, Rutten FH, Mosterd A, Hoes AW. Epidemiology of heart failure. Eur. J. Heart Fail. 22(8), 1342–1356 (2020).
MedlineGoogle Scholar
3. Gerber Y, Weston SA, Redfield MM et al. A contemporary appraisal of the heart failure epidemic in Olmsted County, Minnesota, 2000 to 2010. JAMA Int. Med. 175(6), 996–1004 (2015).
MedlineGoogle Scholar
4. O'Connor CM, Miller AB, Blair JE et al. Causes of death and rehospitalization in patients hospitalized with worsening heart failure and reduced left ventricular ejection fraction: results from Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptam (EVEREST) program. Am. Heart J. 159(5), 841–849 (2010).
MedlineGoogle Scholar
5. Gracia E, Singh P, Collins S, Chioncel O, Pang P, Butler J. The vulnerable phase of heart failure. Am. J. Ther. 25(4), e456–e464 (2018).
MedlineGoogle Scholar
6. McDonagh T, Metra M, Adamo M et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J. 42(36), 3599–3726 (2021).
Medline CASGoogle Scholar
7. McMurray JJV, Solomon SD, Inzucchi SE et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N. Engl. J. Med. 381(21), 1995–2008 (2019). •• The addition of dapagliflozin to standard therapy in patients with heart failure with reduced ejection fraction (HFrEF) translates into a significant reduction in the risk of cardiovascular death or heart failure (HF) hospitalization.
Medline CASGoogle Scholar
8. Packer M, Anker SD, Butler J et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N. Engl. J. Med. 383(15), 1413–1424 (2020). •• The addition of empagliflozin to standard therapy in patients with HFrEF translates into a significant reduction in the risk of cardiovascular death or HF hospitalization.
Medline CASGoogle Scholar
9. Bhatt DL, Szarek M, Steg PG et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N. Engl. J. Med. 384(2), 117–128 (2021).
Medline CASGoogle Scholar
10. Muscoli S, Barillà F, Tajmir R et al. The new role of SGLT2 inhibitors in the management of heart failure: current evidence and future perspective. Pharmaceutics 14(8), 1730 (2022).
Medline CASGoogle Scholar
11. Vaduganathan M, Greene SJ, Zhang S et al. Projected clinical benefits of implementation of SGLT-2 inhibitors among Medicare beneficiaries hospitalized for heart failure. J. Card. Fail. 28(4), 554–563 (2022).
MedlineGoogle Scholar
12. Montero-Pérez-Barquero M, Escobar Cervantes C, Davila Ramos MF et al. Benefits of dapagliflozin in the whole spectrum of heart failure in clinical practice. The RICA registry. Future Cardiol. 19(6), 323–332 (2023).
Google Scholar
13. Montero-Pérez-Barquero M, Escobar Cervantes C, Llacer P et al. Projected clinical benefits of dapagliflozin in patients with heart failure with preserved ejection fraction. Future Cardiol. 19(6), 333–342 (2023).
CASGoogle Scholar
14. Chivite D, Formiga F, Corbella X et al. Basal functional status predicts one-year mortality after a heart failure hospitalization in elderly patients – the RICA prospective study. Int. J. Cardiol. 254, 182–188 (2018).
MedlineGoogle Scholar
15. Chivite D, Franco J, Formiga F et al. The short-term prognostic value of C-reactive protein in elderly patients with acute heart failure. Rev. Clin. Esp. (Barc.) 219(1), 10–17 (2019).
Medline CASGoogle Scholar
16. Ponikowski P, Voors AA, Anker SD et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J. 37(27), 2129–2200 (2016).
MedlineGoogle Scholar
17. Levey AS, Bosch JP, Lewis JB. Modification of diet in renal disease study group. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann. Int. Med. 130, 461–470 (1999).
Medline CASGoogle Scholar
18. EMA. Dapagliflozin: summary of product characteristics (2022). www.ema.europa.eu/en/documents/product-information/forxiga-epar-product-information_en.pdf
Google Scholar
19. Wei Y, Royston P. Reconstructing time-to-event data from published Kaplan–Meier curves. Stata J. 17(4), 786–802 (2017).
MedlineGoogle Scholar
20. Collett D. Modelling Survival Data in Medical Research. Chapman & Hall/CRC Texts in Statistical Science (2014).
Google Scholar
21. Trullàs JC, Miró Ò, Formiga F et al. The utility of heart failure registries: a descriptive and comparative study of two heart failure registries. Postgrad. Med. J. 92(2087), 260–266 (2016).
MedlineGoogle Scholar
22. Escobar C, Varela L, Palacios B et al. Costs and healthcare utilisation of patients with heart failure in Spain. BMC Health Serv. Res. 20(1), 964 (2020). • Healthcare costs associated with HF are huge, with HF-related hospitalizations being the main determinant.
MedlineGoogle Scholar
23. Crespo-Leiro MG, Segovia-Cubero J, González-Costello J et al. Adherence to the ESC heart failure treatment guidelines in Spain: ESC heart failure long-term registry. Rev. Esp. Cardiol. (Engl. Ed.) 68(9), 785–793 (2015).
MedlineGoogle Scholar
24. Greene SJ, Butler J, Albert NM et al. Medical therapy for heart failure with reduced ejection fraction: the CHAMP-HF registry. J. Am. Coll. Cardiol. 72(4), 351–366 (2018).
MedlineGoogle Scholar
25. Xiang B, Yu Z, Zhou X. Comparative efficacy of medical treatments for chronic heart failure: a network meta-analysis. Front. Cardiovasc. Med. 8, 787810 (2022).
MedlineGoogle Scholar
26. Thorvaldsen T, Ferrannini G, Mellbin L et al. Eligibility for dapagliflozin and empagliflozin in a real-world heart failure population. J. Card. Fail. 28(7), 1050–1062 (2022).
MedlineGoogle Scholar
27. Håkansson E, Norberg H, Själander S, Lindmark K. Eligibility of dapagliflozin and empagliflozin in a real-world heart failure population. Cardiovasc. Ther. 2021, 1894155 (2021). • In clinical practice, a substantial number of patients with HF would benefit from treatment with SGLT2 inhibitors.
MedlineGoogle Scholar
28. Vaduganathan M, Greene SJ, Zhang S et al. Applicability of US Food and Drug Administration labeling for dapagliflozin to patients with heart failure with reduced ejection fraction in US clinical practice: the Get With the Guidelines-Heart Failure (GWTG-HF) registry. JAMA Cardiol. 6(3), 1–10 (2020).
MedlineGoogle Scholar
29. Martinez FA, Serenelli M, Nicolau JC et al. Efficacy and safety of dapagliflozin in heart failure with reduced ejection fraction according to age: insights from DAPA-HF. Circulation 141(2), 100–111 (2020). • In DAPA-HF, the relative benefits of dapagliflozin were independent of age.
Medline CASGoogle Scholar
30. Butt JH, Dewan P, Merkely B et al. Efficacy and safety of dapagliflozin according to frailty in heart failure with reduced ejection fraction: a post hoc analysis of the DAPA-HF trial. Ann. Intern. Med. 175(6), 820–830 (2022).
MedlineGoogle Scholar
31. Mantovani A, Grani G, Chioma L et al. Severe hypoglycemia in patients with known diabetes requiring emergency department care: a report from an Italian multicenter study. J. Clin. Transl. Endocrinol. 5, 46–52 (2016).
MedlineGoogle Scholar

Vol. 19, No. 6

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History

Received 25 January 2023

Accepted 31 May 2023

Published online 29 June 2023

Published in print May 2023

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fca-2023-0016

Acknowledgments

The authors gratefully acknowledge the contributions of all investigators who form part of the Registro Nacional de Insuficiencia Cardíaca registry.

Financial & competing interests disclosure

This study had an unrestricted grant from AstraZeneca Farmacéutica Spain. AstraZeneca Farmacéutica Spain did not have any influence in the collection, analysis or interpretation of the data. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

AstraZeneca Farmacéutica Spain provided writing assistance.

Ethical conduct of research

The registry was approved by the ethics committee of the University Hospital Reina Sofia (Córdoba, Spain). All patients provided written informed consent before being included in the registry.

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