Empagliflozin improves outcomes in HFpEF patients irrespective of age: The EMPEROR-Preserved trial

30 Sep 2022


The article title ”Empagliflozin reduces the risk of death in HFpEF patients irrespective of age: The EMPEROR-Preserved trial" was incorrectly stated. The correct title should be "Empagliflozin improves outcomes in HFpEF patients irrespective of age: The EMPEROR-Preserved trial"*
*According to the published data, empagliflozin did not have a significant effect on the mortality outcomes with no interaction by age. The relative risk reduction of the primary composite outcome (i.e. heart failure hospitalization or cardiovascular death) of empagliflozin was shown to be similar across different age groups (p for trend=0.33).
The editors apologize for this error.

Recently, the effects of empagliflozin and placebo have been compared in patients with heart failure with preserved ejection fraction (HFpEF), taking age as an account of adverse events (AEs) in the EMPEROR-Preserved trial.1 The results showed that empagliflozin reduced first heart failure hospitalization (HFH) and recurrent HFH.1 The efficacy in different age groups was similar.1 In addition, estimated glomerular filtration rate (eGFR) and health-related quality of life (HRQoL) were investigated.1 It also showed significant efficacy across all age groups on these aspects.1

Heart failure (HF) affects around 26 million people worldwide, excluding those probable misdiagnosed and undiagnosed cases.2 About 50% of HF cases have an HFpEF.2 Empagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor indicated for type 2 diabetic patients, which helps lower the blood sugar levels under proper dietary control and exercise.3 It is also found to alleviate the conditions of patients with HF with reduced ejection fraction (HFrEF) or HFpEF, as well as their HFH needs.1

In the EMPEROR-Preserved trial, randomized patients (n=5,988) with the New York Heart Association (NYHA) functional class II-IV HF and ejection fraction >40% were recruited to receive empagliflozin 10mg or placebo medications daily on a double-blind therapy in 1:1 ratio.1 The primary endpoint of the composite of examined cardiovascular death or HFH was demarcated as the time to the first event.1 There were 2 secondary endpoints, and that the first of which was all investigated hospitalizations for first or recurrent HF occurred.1 Joint frailty model accounting for informative censoring was used.1 The cumulative incidence function of the combined primary outcome was measured with age groups <65 years, 65-74 years, 75-79 years and ≥80 years.1 Hazard ratio (95% Cl) as a continuous variable and incidence rate per 100 patient years (95% Cl) was investigated.1 The reduction in relative risks on the primary outcome (p for trend=0.33) and first HFH (p for trend=0.22) by empagliflozin was similar among the age groups.1 The treatment effect on the 4 age groups was maintained for the primary outcome with similar results observed for first and recurrent HFH.1

Furthermore, eGFR of patients was particularly followed up throughout the trial until the study medication was stopped for the assessment of clinical outcomes as another secondary endpoint.1 There were no notable treatment effects on mortality outcomes of empagliflozin for reducing cardiovascular death or HFH, and age did not play a noteworthy role.1 However, the slope of eGFR decline was reduced from week 4 till all the follow-ups were done, and the mean slope of change was 1.36 when compared with placebo.1 The Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 was used to measure HRQoL.1 Patients on empagliflozin medication were found to have greater improvements in the mean KCCQ with minimal differences among the age groups included than those with the placebo treatment.1

The effect of age was measured by the calculation of incidence rates for major endpoints in patients under the placebo treatment.1 Age was found not to affect HFH, but was significantly associated with cardiovascular death (p for trend=0.003).1 Higher age category in the population of the trial had higher blood pressure and left ventricular ejection fraction at baseline, but with a lower eGFR.1 The effectiveness of the drug was not diminished in HFpEF patients ≥75 years and ≥ 85 years.1 Also, the risk of AEs was not significant with increasing age.1

In conclusion, the EMPEROR-Preserved trial indicated the beneficial effects of empagliflozin on patients with HF and HFpEF in all age groups.1

  1. Böhm M et al. Empagliflozin Improves Outcomes in Patients With Heart Failure and Preserved Ejection Fraction Irrespective of Age. J Am Coll Cardiol. 2022 Jul, 80 (1) 1-18.
  2. Toth, P. P., & Gauthier, D. Heart failure with preserved ejection fraction: Strategies for disease management and emerging therapeutic approaches. Postgraduate Medicine, 133(2), 125-139.
  3. Jardiance Hong Kong Prescribing Information.