Effects of empagliflozin on risk for cardiovascular death and heart failure hospitalization across the spectrum of heart failure risk in the EMPA-REG OUTCOME® trial

Eur Heart J. 2018 Feb 1;39(5):363-370. doi: 10.1093/eurheartj/ehx511.


Aims: Empagliflozin reduced the risk of cardiovascular (CV) death and heart failure (HF) hospitalizations in patients with type 2 diabetes (T2D) and established CV disease (CVD) in the EMPA-REG OUTCOME® trial. We investigated whether the benefit of empagliflozin was observed across the spectrum of HF risk.

Methods and results: Seven thousand and twenty patients with T2D (HbA1c 7-10% and eGFR > 30 mL/min/1.73 m2) were treated with empagliflozin 10 or 25 mg, or placebo once daily and followed for median 3.1 years. In patients without HF at baseline (89.9%), we derived the 5-year risk for incident HF using the 9-variable Health ABC HF Risk score [classified as low-to-average (<10%), high (10-20%), and very high (≥ 20%)]. Overall, 67.2% of the population had low-to-average, 24.2% high, and 5.1% very high 5-year HF risk. Across these groups, the effect on CV death and HF hospitalization with empagliflozin was consistent [hazard ratio 0.71 (95% confidence interval: 0.52, 0.96), 0.52 (0.36, 0.75), and 0.55 (0.30, 1.00), respectively]. Effects on CV death in the ostensibly highest HF risk group (HF at baseline and/or incident HF during the trial) in whom 37.9% of the overall CV deaths occurred, was also beneficial [0.67 (0.47, 0.97)], yet, similar benefits were seen in the lower risk patients.

Conclusion: In patients with T2D and established CVD, a sizeable proportion without HF at baseline are at high or very high risk for HF outcomes, indicating the need for active case finding in this patient population. Empagliflozin consistently improved HF outcomes both in patients at low or high HF risk.

Keywords: Cardiovascular disease; Heart failure; Hospitalization; Mortality; Type 2 diabetes.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Benzhydryl Compounds / adverse effects*
  • Benzhydryl Compounds / therapeutic use
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / mortality
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / epidemiology
  • Female
  • Glucosides / adverse effects*
  • Glucosides / therapeutic use
  • Heart Failure* / complications
  • Heart Failure* / mortality
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Middle Aged
  • Risk Factors
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects*
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use
  • Treatment Outcome


  • Benzhydryl Compounds
  • Glucosides
  • Sodium-Glucose Transporter 2 Inhibitors
  • empagliflozin