Efficacy of dapagliflozin in heart failure with reduced ejection fraction according to body mass index

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  • Carly Adamson
  • Pardeep S Jhund
  • Kieran F Docherty
  • Jan Bělohlávek
  • Chern-En Chiang
  • Mirta Diez
  • Jarosław Drożdż
  • Andrej Dukát
  • Jonathan Howlett
  • Charlotta E A Ljungman
  • Mark C Petrie
  • Silvio E Inzucchi
  • Mikhail N Kosiborod
  • Felipe A Martinez
  • Piotr Ponikowski
  • Marc S Sabatine
  • Scott D Solomon
  • Olof Bengtsson
  • Anna Maria Langkilde
  • Daniel Lindholm
  • Mikaela Sjöstrand
  • John J V McMurray

Aims: In heart failure with reduced ejection fraction (HFrEF), there is an ‘obesity paradox’, where survival is better in patients with a higher body mass index (BMI) and weight loss is associated with worse outcomes. We examined the effect of a sodium–glucose co-transporter 2 inhibitor according to baseline BMI in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). Methods and results: Body mass index was examined using standard categories, i.e. underweight (<18.5 kg/m2); normal weight (18.5–24.9 kg/m2); overweight (25.0–29.9 kg/m2); obesity class I (30.0–34.9 kg/m2); obesity class II (35.0–39.9 kg/m2); and obesity class III (≥40 kg/m2). The primary outcome in DAPA-HF was the composite of worsening heart failure or cardiovascular death. Overall, 1348 patients (28.4%) were under/normal-weight, 1722 (36.3%) overweight, 1013 (21.4%) obesity class I and 659 (13.9%) obesity class II/III. The unadjusted hazard ratio (95% confidence interval) for the primary outcome with obesity class 1, the lowest risk group, as reference was: under/normal-weight 1.41 (1.16–1.71), overweight 1.18 (0.97–1.42), obesity class II/III 1.37 (1.10–1.72). Patients with class I obesity were also at lowest risk of death. The effect of dapagliflozin on the primary outcome and other outcomes did not vary by baseline BMI, e.g. hazard ratio for primary outcome: under/normal-weight 0.74 (0.58–0.94), overweight 0.81 (0.65–1.02), obesity class I 0.68 (0.50–0.92), obesity class II/III 0.71 (0.51–1.00) (P-value for interaction = 0.79). The mean decrease in weight at 8 months with dapagliflozin was 0.9 (0.7–1.1) kg (P < 0.001). Conclusion: We confirmed an ‘obesity survival paradox’ in HFrEF. We showed that dapagliflozin was beneficial across the wide range of BMI studied. Clinical Trial Registration: ClinicalTrials.gov NCT03036124.

Original languageEnglish
JournalEuropean Journal of Heart Failure
Volume23
Issue number10
Pages (from-to)1662-1672
Number of pages11
ISSN1388-9842
DOIs
Publication statusPublished - 2021

Bibliographical note

Publisher Copyright:
© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

    Research areas

  • Adiposity, Body mass index, Dapagliflozin, Heart failure, Obesity, SGLT2 inhibitor

ID: 303042186