EMPEROR reduced – cardiac and renal targets with empagliflozin in patients with heart failure with reduced ejection fraction

Authors: Špinar J.;  Špinarová L.;  Vítovec J.
Authors‘ workplace: Interní kardioangiologická klinika LF MU a FN u sv. Anny v Brně
Published in: Kardiol Rev Int Med 2020, 22(3): 118-122


Background: In patients with type 2 diabetes and in those with primarily mild heart failure with and without diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of serious heart failure (HF) events. More evidence is needed regarding the effects of SGLT2 inhibitors in patients across the broad spectrum of HF, including those with markedly reduced ejection fraction and higher natriuretic peptide levels, regardless of the presence of diabetes.

Methods: In this phase III, placebo-controlled trial, we randomly assigned 3,730 patients with New York Heart Association class II, III, or IV HF and an ejection fraction of 40 % or less to receive either empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes and hospitalization for worsening heart failure. Another secondary enpoint was effect on renal functions.

Results: Over a median of 16 months, the primary outcome occurred in 361 of 1,863 patients (19.4%) in the empagliflozin group and in 462 of 1,867 patients (24.7%) in the placebo group (HR 0.75; 95% CI, 0.65 to 0.86; P<0.001). The effect of empagliflozin on the primary outcome was consistent in patients with and without diabetes and in those taking and not taking sacubitril/valsartan. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (HR 0.70; 95% CI, 0.58 to 0.85; P<0.001). The rate of decline in eGFR was slower in the empagliflozin group than in the placebo group (–0.2 ml/min/1.73m2/year vs. –2.3 ml/min/1.73m2/year; P < 0.001), and was accompanied by a lower frequency of serious renal outcomes. The frequency of adverse events related to hypotension, renal dysfunction and hypoglycemia did not differ between treatment groups.

Conclusions: Among a broad spectrum of patients with HF and a reduced ejection fraction, empagliflozin reduced the risk of death from cardiovascular causes or hospitalization for HF, regardless of the presence or absence of diabetes and background therapy for HF.


empagliflozin – heart failure – diabetes mellitus


1. Lo KB, Gul F, Ram P, Kluger AY et al. The effects of SGLT2 inhibitors on cardiovascular and renal outcomes in diabetic patients: a systematic review and meta-analysis. Cardiorenal Med 2020; 10 (1): 1–10. doi: 10.1159/000503919.

2. Kato ET, Silverman MG, Mosenzon O et al. Effect of dapagliflozin on heart failure and mortality in type 2 diabetes mellitus. Circulation 2019; 139 (22): 2528–2536. doi: 10.1161/CIRCULATIONAHA.119.040130.

3. Neuen BL, Young T, Heerspink HJ et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 2019; 7 (11): 845–854. doi: 10.1016/S2213-8587 (19) 30256-6.

4. Packer M. SGLT2 inhibitors produce cardiorenal benefits by promoting adaptive cellular reprogram­ming to induce a state of fasting mimicry: a paradigm shift in understanding their mechanism of action. Diabetes Care 2020; 43 (3): 508–511. doi: 10.2337/dci19-0074.

5. McMurray JJ, Solomon SD, Inzucchi SE et al. DAPA-HF Trial Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 2019; 381: 1995–2008. doi: 10.1056/NEJMoa1911303.

6. Packer M, Anker SD, Butler J et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. NEJM 2020. Online ahead of print. doi: 10.1056/NEJMoa2022190.

Paediatric cardiology Internal medicine Cardiac surgery Cardiology
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