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Baseline Characteristics of Patients With HF With Mildly Reduced and Preserved Ejection Fraction: DELIVER TrialOpen Access

Clinical Research

J Am Coll Cardiol HF, 10 (3) 184–197
Sections

Central Illustration

Abstract

Objectives

This report describes the baseline clinical profiles and management of DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial participants and how these compare with those in other contemporary heart failure with preserved ejection fraction trials.

Background

The DELIVER trial was designed to evaluate the effects of the sodium-glucose cotransporter–2 inhibitor dapagliflozin on cardiovascular death, heart failure (HF) hospitalization, or urgent HF visits in patients with HF with mildly reduced and preserved left ventricular ejection fraction (LVEF).

Methods

Adults with symptomatic HF and LVEF >40%, with or without type 2 diabetes mellitus, elevated N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels, and evidence of structural heart disease were randomized to dapagliflozin 10 mg once daily or matching placebo.

Results

A total of 6,263 patients were randomized (mean age: 72 ± 10 years; 44% women; 45% type 2 diabetes mellitus; 45% with body mass index ≥30 kg/m2; and 57% with history of atrial fibrillation or flutter). Most participants had New York Heart Association functional class II symptoms (75%). Baseline mean LVEF was 54.2 ± 8.8% and median NT-proBNP of 1,399 pg/mL (IQR: 962 to 2,210 pg/mL) for patients in atrial fibrillation/flutter compared with 716 pg/mL (IQR: 469 to 1,281 pg/mL) in those who were not. Patients in both hospitalized and ambulatory settings were enrolled, including 10% enrolled in-hospital or within 30 days of a hospitalization for HF. Eighteen percent of participants had HF with improved LVEF.

Conclusions

DELIVER is the largest and broadest clinical trial of this population to date and enrolled high-risk, well-treated patients with HF with mildly reduced and preserved LVEF. (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [ NCT03619213])

References

  • 1. Solomon S.D., Vaduganathan M., Claggett B.L., et al. "Sacubitril/valsartan across the spectrum of ejection fraction in heart failure". Circulation 2020. 352-361.

    CrossrefMedlineGoogle Scholar
  • 2. Solomon S.D., Claggett B., Lewis E.F., et al. "Influence of ejection fraction on outcomes and efficacy of spironolactone in patients with heart failure with preserved ejection fraction". Eur Heart J 2016;37:455-462.

    CrossrefMedlineGoogle Scholar
  • 3. Solomon S.D., Anavekar N., Skali H., et al. "Influence of ejection fraction on cardiovascular outcomes in a broad spectrum of heart failure patients". Circulation 2005;112:3738-3744.

    CrossrefMedlineGoogle Scholar
  • 4. Wilcox J.E., Fang J.C., Margulies K.B., Mann D.L. "Heart failure with recovered left ventricular ejection fraction: JACC scientific expert panel". J Am Coll Cardiol 2020. 719-734.

    View ArticleGoogle Scholar
  • 5. Basuray A., French B., Ky B., et al. "Heart failure with recovered ejection fraction clinical description, biomarkers, and outcomes". Circulation 2014;129:2380-2387.

    CrossrefMedlineGoogle Scholar
  • 6. Bozkurt B., Coats A.J.S., Tsutsui H., et al. "Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association". Eur J Heart Fail 2021;23:352-380.

    CrossrefMedlineGoogle Scholar
  • 7. Solomon S.D., de Boer R.A., DeMets D., et al. "Dapagliflozin in heart failure with preserved and mildly reduced ejection fraction: rationale and design of the DELIVER trial". Eur J Heart Fail 2021;23:1217-1225.

    CrossrefMedlineGoogle Scholar
  • 8. Solomon S.D., Rizkala A.R., Lefkowitz M.P., et al. "Baseline characteristics of patients with heart failure and preserved ejection fraction in the PARAGON-HF trial". Circ Hear Fail 2018;11.

    Google Scholar
  • 9. McMurray J., Östergren J., Pfeffer M., et al. "Clinical features and contemporary management of patients with low and preserved ejection fraction heart failure: baseline characteristics of patients in the Candesartan in Heart failure – Assessment of Reduction in Mortality and morbidity (CHARM) program". Eur J Heart Fail 2003;5:261-270.

    CrossrefMedlineGoogle Scholar
  • 10. Anker S.D., 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;22:2383-2392.

    CrossrefMedlineGoogle Scholar
  • 11. Shah S.J., Heitner J.F., Sweitzer N.K., et al. "Baseline characteristics of patients in the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial". Circ Hear Fail 2013;6:184-192.

    CrossrefMedlineGoogle Scholar
  • 12. McMurray J.J.V., Carson P.E., Komajda M., et al. "Heart failure with preserved ejection fraction: Clinical characteristics of 4133 patients enrolled in the I-PRESERVE trial". Eur J Heart Fail 2008;10:149-156.

    CrossrefMedlineGoogle Scholar
  • 13. Anker S.D., Butler J., Filippatos G., et al. "Empagliflozin in heart failure with a preserved ejection fraction". N Engl J Med 2021;385:1451-1461.

    CrossrefMedlineGoogle Scholar
  • 14. Packer M., Butler J., Zannad F., et al. "Empagliflozin and major renal outcomes in heart failure". N Engl J Med 2021;385:1531-1533.

    CrossrefMedlineGoogle Scholar
  • 15. Packer M., Butler J., Filippatos G., et al. "Design of a prospective patient-level pooled analysis of two parallel trials of empagliflozin in patients with established heart failure". Eur J Heart Fail 2020;22:2393-2398.

    CrossrefMedlineGoogle Scholar
  • 16. Lam C.S.P., Solomon S.D. "Classification of heart failure according to ejection fraction: JACC review topic of the week". J Am Coll Cardiol 2021. 3217-3225.

    View ArticleGoogle Scholar
  • 17. McDonagh T.A., Metra M., Adamo M., et al. "2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure". Eur Heart J 2021;42:36: 3599-3726. https://doi.org/10.1093/eurheartj/ehab368.

    CrossrefMedlineGoogle Scholar
  • 18. Fudim M., Kelly J.P., Brophy T.J., et al. "Trends in Treatment for Patients Hospitalized with Heart Failure with Preserved Ejection Fraction Before and After Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT)". Am J Cardiol 2020;125:1655-1660.

    CrossrefMedlineGoogle Scholar
  • 19. Solomon S.D., Rizkala A.R., Gong J., et al. "Angiotensin receptor neprilysin inhibition in heart failure with preserved ejection fraction: rationale and design of the PARAGON-HF trial". J Am Coll Cardiol HF 2017;5:7: 471-482. https://doi.org/10.1016/j.jchf.2017.04.013.

    Google Scholar
  • 20. Bhatt D.L., Szarek M., Steg P.G., et al. "Sotagliflozin in patients with diabetes and recent worsening heart failure". N Engl J Med 2021;384:117-128.

    CrossrefMedlineGoogle Scholar
  • 21. Anker S.D., Butler J., Filippatos G.S., 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;21:1279-1287.

    CrossrefMedlineGoogle Scholar
  • 22. Wohlfahrt P., Nativi-Nicolau J., Zhang M., et al. "Quality of life in patients with heart failure with recovered ejection fraction". JAMA Cardiol 2021;6:8: 957-962.

    CrossrefMedlineGoogle Scholar
  • 23. Merlo M., Stolfo D., Anzini M., et al. "Persistent recovery of normal left ventricular function and dimension in idiopathic dilated cardiomyopathy during long-term follow-up: does real healing exist?"J Am Heart Assoc 2015;4: e001504.

    CrossrefGoogle Scholar
  • 24. Tromp J., Claggett B.L., Liu J., et al. "Global differences in heart failure with preserved ejection fraction: the PARAGON-HF trial". Circ Hear Fail 2021;14:4: e007901.

    MedlineGoogle Scholar
  • 25. Tromp J., Teng T.H., Tay W.T., et al. "Heart failure with preserved ejection fraction in Asia". Eur J Heart Fail 2019;21:23-36.

    CrossrefMedlineGoogle Scholar
  • 26. Morris A.A., Testani J.M., Butler J. "Sodium-glucose cotransporter-2 inhibitors in heart failure: racial differences and a potential for reducing disparities". Circulation 2021. 2329-2331.

    CrossrefMedlineGoogle Scholar