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.
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%.
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.
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.
Packer M, Anker SD, Butler J, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190. Epub ahead of print. PMID: 32865377.
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
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.