Dapagliflozin benefit in HFrEF: improved outcomes, diabetes or not

  • Petrie MC & al.
  • JAMA
  • 27 Mar 2020

  • curated by Miriam Tucker
  • Clinical Essentials
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Takeaway

  • Dapagliflozin is linked to reduced cardiovascular morbidity and mortality in patients who have heart failure (HF) with reduced ejection fraction (rEF), regardless of diabetes status.

Why this matters

  • A key question is whether sodium-glucose cotransporter-2 inhibitors offer benefit in patients with HFrEF without diabetes.

Study design

  • Exploratory analysis of phase 3 randomized trial involving 4744 patients with HF. 
  • 55% did not have diabetes.
  • Patients were randomly assigned to 10 mg/day dapagliflozin or placebo plus usual therapy.
  • Primary outcome was composite of worsening HF episode or cardiovascular death.
  • Funding: AstraZeneca.

Key results

  • Primary composite outcome:
    • In patients without diabetes: 
      • 13.2% with dapagliflozin vs 17.7% with placebo;
      • HR, 0.73 (95% CI, 0.60-0.88). 
    • In patients with diabetes:
      • 20.0% dapagliflozin vs 25.5% placebo;
      • HR, 0.75 (95% CI, 0.63-0.90). 
    • Pinteraction=.80.
  • In those without diabetes, rates of the primary endpoint with: 
    • HbA1c ≥5.7% (i.e., prediabetes): 
      • 13.7% dapagliflozin vs 18.0% placebo; 
      • HR, 0.74 (95% CI, 0.59-0.94). 
    • HbA1c
    • 12.1% dapagliflozin vs 16.9% placebo; 
    • HR, 0.67 (95% CI, 0.47-0.96).
  • Pinteraction=.72.  
  • No difference in the effect of dapagliflozin on other outcomes with vs without diabetes.
  • Adverse events related to volume depletion and kidney impairment did not differ between groups or by diabetes status.
  • With dapagliflozin, 3 patients (0.06%) experienced definite/probable diabetic ketoacidosis.
  • Limitations

    • Subgroup analyses, some post hoc.