Empagliflozin (4) – Jardiance®

• Clinical trials
  • To assess the additional benefit of empagliflozin, the pharmaceutical manufacturer cites the placebo-controlled, double-blind, randomised EMPEROR-Preserved trial, in which patients with chronic heart failure in NYHA classes II to IV with preserved ejection fraction, defined as LVEF > 40 per cent, were studied.

a) Adults with symptomatic, chronic heart failure with preserved ejection fraction (HFpEF; LVEF > 50 %) and with mildly reduced ejection fraction (HFmrEF; LVEF > 40 to 49 %)

• Hint for a minor additional benefit
• Due to the uncertainties described above, the certainty of the evidence is classified as ‘hint’.
• mortality
  • There are no statistically significant differences between the treatment arms for either the endpoint ‘all-cause mortality’ or the additional endpoint ‘cardiovascular death’.
• Morbidity – hospitalisation due to heart failure
  • For the endpoint ‘hospitalisation due to heart failure’ for the period up to the first event, there is a statistically significant advantage in favour of empagliflozin compared with the comparator arm.
  • For the operationalisation ‘including repeated events’, there is also a statistically significant advantage for empagliflozin compared with the comparator arm.
• Morbidity – total hospitalisation
  • For the endpoint ‘total hospitalisation’ for the time to first event, the EMPEROR-Preserved study showed a statistically significant advantage for empagliflozin compared with the control arm.
  • For the operationalisation of ‘including recurrent events’, no statistically significant advantage was observed in favour of empagliflozin compared with the control arm.
• Morbidity – myocardial infarction and stroke
  • For the endpoints ‘myocardial infarction’ and ‘stroke’, no statistically significant differences were observed between the treatment arms.
  • For the endpoint ‘myocardial infarction’, there is an effect modification by the characteristic of sex. In women, there is a statistically significant difference in favor of empagliflozin that is a disadvantage. In men, there are no statistically significant differences.
• Morbidity – Acute kidney injury
  • For the endpoint ‘acute kidney injury’ (PT), a statistically significant advantage was observed between the treatment arms in favour of empagliflozin over the comparator arm.
• Morbidity – Renal morbidity
  • There was no statistically significant difference between the treatment arms, either for the combined renal endpoint or for the respective individual components.
• health status
  • No statistically significant difference was observed between the treatment arms for an improvement of ≥ 15 points at week 52.
• Health-related quality of life
  • There were no statistically significant differences between the treatment arms for the clinical total score (KCCQ-OSS), operationalised as an improvement of ≥ 15%.
• Side effects – Serious adverse events (SAE)
  • For the SAE endpoint, there was a statistically significant advantage for empagliflozin compared with the control group.
• Side effects – Discontinuation due to adverse events (AE)
  • No statistically significant differences were observed between the treatment groups for the endpoint of discontinuation due to AEs.
• Side effects – Specific adverse events
  • In detail, for the specific AEs urinary tract infection (PT, AE), hypertensive crisis (PT, SAE) and basal cell carcinoma (PT, SAE), a statistically significant advantage was observed between the treatment groups in favour of empagliflozin compared with the control group.
  • In detail, for the specific AEs metabolic and nutritional disorders (SOC, SAE), musculoskeletal, connective tissue and bone disorders (SOC; SAE), disorders of the blood and lymphatic system (SOC, SAE) and disorders of the respiratory tract, thoracic cavity and mediastinum (SOC, SAE), a statistically significant advantage was observed between the treatment groups in favour of empagliflozin compared with the control group.
  • In detail, no statistically significant difference was observed between the treatment groups for the specific AE categories ‘Diseases of the genital organs and mammary glands’ (SOC, UE) and ‘Diabetic ketoacidosis’ (PT, UE).

Courtesy translation only, please refer to the German original.