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Initial Decline (Dip) in Estimated Glomerular Filtration Rate After Initiation of Dapagliflozin in Patients With Heart Failure and Reduced Ejection Fraction: Insights from DAPA-HF

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  • Carly Adamson
  • Kieran F Docherty
  • Hiddo J L Heerspink
  • Rudolf A de Boer
  • Kevin Damman
  • Silvio E Inzucchi
  • Lars Køber
  • Mikhail N Kosiborod
  • Felipe A Martinez
  • Mark C Petrie
  • Piotr Ponikowski
  • Marc S Sabatine
  • Morten Schou
  • Scott D Solomon
  • Subodh Verma
  • Olof Bengtsson
  • Anna Maria Langkilde
  • Mikaela Sjöstrand
  • Muthiah Vaduganathan
  • Pardeep S Jhund
  • John J V McMurray
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BACKGROUND: In a post hoc analysis, the frequency of occurrence of an early decline (dip) in estimated glomerular filtration rate (eGFR) after initiation of dapagliflozin and its association with outcomes were evaluated in patients with heart failure and reduced ejection fraction randomized in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial.

METHODS: Patients with heart failure with reduced ejection fraction with or without type 2 diabetes and an eGFR ≥30 mL·min-1·1.73 m-2 were randomized to placebo or dapagliflozin 10 mg daily. The primary outcome was the composite of worsening heart failure or cardiovascular death. The extent of the dip in eGFR between baseline and 2 weeks, patient characteristics associated with a >10% decline, and cardiovascular outcomes and eGFR slopes in participants experiencing this decline were investigated. Time-to-event outcomes were assessed in Cox regression from 14 days; eGFR slopes were assessed with repeated-measures mixed-effect models.

RESULTS: The mean change in eGFR between day 0 and 14 was -1.1 mL·min-1·1.73 m-2 (95% CI, -1.5 to -0.7) with placebo and -4.2 mL·min-1·1.73 m-2 (95% CI, -4.6 to -3.9) with dapagliflozin, giving a between-treatment difference of 3.1 mL·min-1·1.73 m-2 (95% CI, 2.6-3.7). The proportions of patients randomized to dapagliflozin experiencing a >10%, >20%, and >30% decline in eGFR were 38.2%, 12.6%, and 3.4%, respectively; for placebo, they were 21.0%, 6.4%, and 1.3%, respectively. The odds ratio for a >10% early decline in eGFR with dapagliflozin compared with placebo was 2.36 (95% CI, 2.07-2.69; P<0.001). Baseline characteristics associated with a >10% decline in eGFR on dapagliflozin were older age, lower eGFR, higher ejection fraction, and type 2 diabetes. The hazard ratio for the primary outcome in patients in the placebo group experiencing a >10% decline in eGFR compared with ≤10% decline in eGFR was 1.45 (95% CI, 1.19-1.78). The corresponding hazard ratio in the dapagliflozin group was 0.73 (95% CI, 0.59-0.91; Pinteraction<0.001). A >10% initial decline in eGFR was not associated with greater long-term decline in eGFR or more adverse events.

CONCLUSIONS: The average dip in eGFR after dapagliflozin was started was small and associated with better clinical outcomes compared with a similar decline on placebo in patients with heart failure with reduced ejection fraction. Large declines in eGFR were uncommon with dapagliflozin.

REGISTRATION: URL: https://www.

CLINICALTRIALS: gov; Unique identifier: NCT03036124.

Original languageEnglish
JournalCirculation
Volume146
Issue number6
Pages (from-to)438-449
Number of pages12
ISSN0009-7322
DOIs
Publication statusPublished - 9 Aug 2022

    Research areas

  • Benzhydryl Compounds/adverse effects, Diabetes Mellitus, Type 2/complications, Glomerular Filtration Rate, Glucosides/adverse effects, Heart Failure/chemically induced, Humans, Ventricular Dysfunction, Left/complications

ID: 78362972