EASD 2020 Highlights

Conference summaries


DIABETES &HF

Empagliflozin for the treatment of chronic heart failure and a reduced ejection fraction in patients with and without diabetes: new results of the EMPEROR-Reduced trial

Presented by:

Javed Butler, MD; Milton Packer, MD; Stefen D. Anker, MD; Gerasimos Filippatos, MD; Faiez Zannad, MD


  • Empagliflozin is superior to placebo in improving heart failure outcomes among patients with symptomatic stable heart failure with reduced ejection fraction.
  • Benefit was seen in a reduction in heart failurehospitalisations, as well as in renal outcomes.
  • The findingsare similar to the DAPA-HF trial for dapagliflozin.

What do we already know about this topic?

  • Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalisation for heart failure in patients regardless of the presence or absence of diabetes.1
  • More evidence is needed regarding the effects of these drugs in patients across the broad spectrum of heart failure, including those with a markedly reduced ejection fraction.

How was this study conducted?

  • Patients with symptomatic heart failure with reduced ejection fraction (NYHA functional class II/III/IV) were randomised in a 1:1 fashion to either empagliflozin 10 mg (n = 1863) or matching placebo (n = 1867); all patients were receiving appropriate treatments for heart failure.
  • The primary outcome was a composite of cardiovascular death or hospitalisation for worsening heart failure.

What does this study add?

  • The primary outcomefor empagliflozin vs. placebo was 19.4% vs. 24.7% (HR 0.75, 95% CI 0.65-0.86, p <0.001), and independent of diabetes status.
  • Cardiovascular death was similar for empagliflozin vs. placebo (10% vs. 10.8%; HR 0.92, 95% CI 0.75-1.12).
  • Hospitalisation for heart failure occurred in 13.2% of patients treated with empagliflozin compared to 18.3% for placebo (HR 0.69, 95% CI 0.59-0.81).
  • Total hospitalisations for heart failure significantly favoured empagliflozin (HR 0.70, 95% CI 0.58-0.85, p =0.0003)
  • The composite renal outcome (chronic haemodialysis, renal transplantation, profound sustained reduction in eGFR) significantly favoured empagliflozin with a rate of 1.6 vs. 3.1 per 100 patient-years (HR 0.50, 95% CI 0.32-0.77, p <0.01)
  • All-cause mortality was not significantly reduced by empagliflozin (13.4% vs. 14.2%; HR 0.92, 95% CI 0.77-1.10, p >0.05)
  • Change in HbA1c between baseline and week 52 (patients with diabetes) was -0.28 vs. -0.12% (p <0.05).
  • Similar rates of severehypoglycaemic events were observed: 1.4% vs. 1.5%.

Perspectives

How does this study impact clinical practice?

  • The 25% decrease in the risk of the composite of cardiovascular death and hospitalization for heart failure with empagliflozin was identical to that seen in DAPA-HF.
  • Although the effect on cardiovascular death in this trial was smaller than that seen in DAPA-HF, the reverse was true when the effects of dapagliflozin and empagliflozin on cardiovascular death were assessed in comparable trials in type 2 diabetes.
  • The effects of these drugs on survival are characterized by significant heterogeneity.


References

References


  1. Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019 Jan 5;393(10166):31-9.

 

Related content



Expert commentary by Prof. Francesco Giorgino

Expert commentary by Prof. Francesco Giorgino

 

Prof. Francesco Giorgino
President, Italian Society of Endocrinology (SIE)
Professor of Endocrinology, Chairman, Department of Emergency and Organ Transplantation
Head, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases
University of Bari Aldo Moro
Chief, Division of Endocrinology, University Hospital Policlinico Consorziale

 

 

The EMPEROR-Reduced is an important study, which assessed the effects of empagliflozin, an SGLT2 inhibitor in patients with heart failure (HF) and reduced ejection fraction (HFrEF), less than 40%. The study was a double-blind, placebo-controlled trial randomizing 3730 patients with Class II to IV HF, with or without diabetes, to receive empagliflozin 10 mg daily or placebo, in addition to standard therapy. During a median follow-up of 16 months, empagliflozin was able to significantly reduce the primary endpoint, a composite of cardiovascular (CV) death or hospitalization for HF by 25% (P< 0.001). The Number Needed to Treat (NNT) was 19 for this outcome, which is a significant achievement, with the effect largely driven by the reduction in hospitalization for HF, rather than CV mortality. In addition, the rate of decline in the estimated glomerular filtration rate (eGFR; a secondary outcome) was significantly slower in empagliflozin-treated patients, who also had a lower risk of serious renal outcomes such as chronic dialysis or renal transplantation or a sustained eGFR reduction of 40% or more. Importantly, these benefits with empagliflozin occurred in patients receiving state-of-the-art therapy for HF, such as angiotensin receptor neprilysin inhibitor (ARNI), and were the same in people with or without diabetes. The only adverse effects were more uncomplicated genital tract infections, whereas issues such as hypotension, volume depletion, renal insufficiency, or hyperkalaemia, which are frequent in these patients were not increased by the treatment with empagliflozin.

The study shows results that are very similar to those in another trial with an SGLT2 inhibitor in individuals with HFrEF, the DAPA-HF trial with dapagliflozin, thus corroborating the efficacy of SGLT2 inhibitors in the clinical context of HF with reduced ejection fraction. Both trials showed an early separation of the curves between the placebo and intervention arms for HF outcomes. Moreover, the ability of SGLT2 inhibitors to reduce such outcome was clearly independent of their effect on hyperglycemia, since similar effects were consistently seen in normoglycemic individuals. However, CV death and all-cause death were unaffected in EMPEROR-Reduced, whereas they were reduced in DAPA-HF. Curiously, the opposite pattern was found with empagliflozin and dapagliflozin in EMPA-REG and DECLARE-TIMI 58, respectively, which enrolled only type 2 diabetic patients with various degrees of CV disease. Therefore, while the benefit on HF outcomes is clearly consistent, that on CV or total death appears to be characterized by a significant level of heterogeneity, not easily explained by the baseline risk of the exposed population: patients were at higher risk in EMPA-REG than in DECLARE-TIMI 58 (100% vs 30% with CV disease), as well as in EMPEROR-Reduced than in DAPA-HF (27% vs. 31% EF, higher natriuretic peptide levels, 20% vs. 11% patients treated with ARNI), yet results on mortality were different. Moreover, while the DAPA-HF excluded patients with eGFR <30mL/min/1.73m2, EMPEROR-Reduced extended the enrolment to eGFR >20mL/min/1.73m2, which is an unprecedented threshold for enrolment and provides evidence of benefit also in patients with severe renal failure.

The two trials provide complementary and reinforcing evidence, confirming the role of SGLT2 inhibitors as

the foundational therapy in HFrEF. The renal benefit is also of interest, given that this population with symptomatic and severe HF is at very high risk for declining of renal function. Improving HFrEF outcomes

in patients with compromised renal function remains an unmet need, and both DAPA-HF and EMPEROR-Reduced make SGLT2 inhibitors an attractive option for patients who have both HF and chronic kidney

disease. Last but not least, both agents were associated with improvements in quality of life, which is very important for patients who suffer not only from the risk of morbidity and mortality, but also from poor quality of life.

 

Prof. Francesco Giorgino
President, Italian Society of Endocrinology (SIE)
Professor of Endocrinology, Chairman, Department of Emergency and Organ Transplantation
Head, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases
University of Bari Aldo Moro
Chief, Division of Endocrinology, University Hospital Policlinico Consorziale

Francesco Giorgino is Professor of Endocrinology and Metabolism and Chairman of the Department of Emergency and Organ Transplantation at the University of Bari Aldo Moro, Bari, Italy. He is also Chief of the Division of Endocrinology at the University Hospital Policlinico Consorziale in Bari, Italy.

Professor Giorgino has received distinguished scientific awards from various international and national institutions, and he has served on many national commissions and national boards, including the Executive Committees and Scientific Committees of the Italian Society of Diabetology and of the Italian Society of Endocrinology. He is currently President of the Italian Society of Endocrinology.

He is or has been a member of the Editorial Boards for the following journals: PLoS ONE, Journal of Endocrinology, EndocrinologyJournal of Endocrinological InvestigationAdipocyteActa Diabetologica, Cardiorenal Medicine, and Diabetes Metabolism Research and Reviews. He has published more than 200 original and review articles in prestigious scientific journals and has been an invited speaker at many national and international meetings.

Professor Giorgino’s research interests include the mechanisms leading to insulin resistance and beta-cell dysfunction in type 2 diabetes with a particular focus on skeletal muscle metabolism and organ cross-talk, inflammation and lipotoxicity, and the effects of diabetes drugs on pancreatic islets and the cardiovascular system.

 

Acknowledgements

This is a highlights summary of an oral session given at the EASD 2020 Virtual Meeting and presented by:

Javed Butler, MD
Dept. of Medicine, University of Mississippi School of Medicine, Jackson, MS, USA

Milton Packer, MD
Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX, USA

Stefen D.Anker, MD
Dept. of Cardiology and BCRT, CharitéCVK, Berlin, Germany

GerasimosFilippatos, MD
National and Kapodistrian University of Athens School of Medicine, Athens University Hospital Attikon, Athens, Greece

Faiez Zannad, MD
Université de Lorraine, Centre d’InvestigationsCliniquesPlurithématique, CHRU de Nancy, France

The presenting authors of the original session had no part in the creation of this conference highlights summary. 

The content is produced by Infomedica. The summary text was drafted by Patrick Moore, PhD, and reviewed by Marco Gallo, MD, an independent external expert, and approved by Florian Toti, MD, the scientific editor of the program.


DIABETES & PREGNANCY

20 years HAPO Study: What have we learned so far?

Presented by: Patrick M. Catalano, MD
Expert commentary by Elizabeth O. Buschur, MD

DIABETES & HF

Empagliflozin for the treatment of chronic heart failure and a reduced ejection fraction in patients with and without diabetes: new results of the EMPEROR-Reduced trial

Presented by: Javed Butler, MD; Milton Packer, MD; Stefen D.Anker, MD; Gerasimos Filippatos, MD; Faiez Zannad, MD
Expert commentary by Prof. Francesco Giorgino

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