Dapagliflozin (8) – Forxiga®

• Clinical trials
  • The double-blind, placebo-controlled, randomised DELIVER trial is available for the assessment of the additional benefit of dapagliflozin.

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

• Hint of 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 dapagliflozin compared with the comparator arm.
  • For the additional operationalisation ‘including repeated events’, there was also a statistically significant advantage for dapagliflozin compared with the comparator arm.
• Morbidity – total hospitalisation
  • For the endpoint ‘total hospitalisation’ for the time to first event, there was no statistically significant difference between dapagliflozin and the comparator arm.
• Morbidity – myocardial infarction and stroke
  • For the endpoints ‘myocardial infarction’ and ‘stroke’, there were no statistically significant differences between the treatment arms in either case.
• Morbidity – Renal morbidity
  • The endpoint ‘renal morbidity’ is therefore presented for supplementary information only. Overall, no statistically significant differences were observed between the treatment arms for this endpoint.
• Health status – EQ-5D VAS
  • There was no statistically significant difference between the treatment arms in terms of an improvement of ≥ 15 points at the final study visit.
• Health status – PGIS
  • For the health status endpoint assessed using the PGIS, there was a statistically significant difference in favour of dapagliflozin compared with the comparator arm. However, this difference is considered to be no more than minor.
• Quality of life – KCCQ-OSS (Overall Summary Score)
  • For the KCCQ-OSS clinical summary score, operationalised as an improvement of ≥ 15%, there is a statistically significant advantage in favour of dapagliflozin compared with the comparator arm.
• Side effects – Serious adverse events (SAEs) and discontinuation due to adverse events (AEs)
  • For the endpoints SAE and discontinuation due to AEs, no statistically significant differences were observed between the treatment arms.
• Side effects – Specific adverse events
  • No suitable data are available for the endpoints urinary tract infection (AE) and genital infection (AE), as non-serious side effects were not systematically recorded in the study and it is known that the majority of these events fall into the category of non-serious side effects.
  • For the endpoint diabetic ketoacidosis, there was no statistically significant difference between the treatment groups.
  • In detail, a statistically significant difference in favour of dapagliflozin compared with the control arm was observed for the specific SAE relating to gastrointestinal tract disorders.
  • Specifically, for the specific SAE COVID-19, a statistically significant disadvantage was observed compared with the control arm for dapagliflozin.
• Overall assessment
  • Taking an overall view of the results, based on the positive effects of dapagliflozin in preventing hospitalisation due to heart failure and in achieving an improvement of ≥ 15 % in the KCCQ-OSS clinical summary score in the health-related quality of life category, a minor additional benefit is inferred for dapagliflozin compared with the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.