The Emperor Finally Has Clothes! Insights from EMPEROR Preserved

Recent randomized controlled trials (RCTs) in heart failure (HF)1,2 have shown that sodium–glucose cotransporter 2 (SGLT2) inhibitors, including empagliflozin and dapagliflozin, can reduce the risk of cardiovascular death (CVD) and heart failure hospitalization (HFH) in patients with heart failure with reduced ejection fraction (HFrEF), irrespective of diabetes status.

The EMPEROR-Preserved RCT evaluated the impact of empagliflozin, in addition to standard care, on major HF outcomes in patients with symptomatic heart failure with preserved ejection fraction (HFpEF, EF >40%). The investigators enrolled nearly 6,000 patients at 622 centers and found that the use of empagliflozin was associated with a lower combined risk of CVD or HFHs than the placebo group (13.8% vs. 17.1%; HR 0.79; 95% CI, 0.69-0.90; P<0.001). This finding was driven by the lower risk of HFH (8.6% vs. 11.8%; HR 0.71; 95% CI, 0.60-0.83) without a reduction in CVD. The effect of empagliflozin on the primary outcome was consistent across prespecified subgroups and no significant differences were found between groups regarding serious adverse events.

The medical management of HFpEF continues to be a challenge and prior RCTs (PARAGON-HF, TOPCAT) had fallen short in achieving their primary endpoints. Given the limited therapeutic options available, these findings offer clinicians a safe intervention to reduce the risk of HFH, in patients with HFpEF. While unable to demonstrate a mortality benefit seen in HFrEF, the Food and Drug Administration has granted empagliflozin Breakthrough Therapy designation,3 and the HF community now enthusiastically awaits the results of DELIVER-HF4 to evaluate the impact of dapagliflozin in HFpEF.


  1. Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med 2020;383:1413-24.
  2. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019;380:347-57.
  3. FDA grants Jardiance® Breakthrough Therapy designation for heart failure with preserved ejection fraction (Lilly website). 2021. Available at: . Accessed 09/15/2021.
  4. Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure. (DELIVER) ( 2021. Available at: Accessed 09/15/2021.

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Lipid Metabolism, Acute Heart Failure

Keywords: ESC Congress, ESC21, Sodium-Glucose Transporter 2 Inhibitors, Heart Failure, Stroke Volume, United States Food and Drug Administration, Glucosides, Benzhydryl Compounds, Ventricular Dysfunction, Left, Sodium-Glucose Transporter 2, Hospitalization, Reference Standards, Diabetes Mellitus

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