AHA 2019 — Dapagliflozin benefits nondiabetic heart failure patients with reduced ejection fraction


  • Daniel M. Keller, Ph.D
  • Conference Reports
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Takeaway

  • DAPA-HF trial: dapagliflozin (DAPA) reduces heart failure (HF) events in patients with reduced left ventricular ejection fraction (HFrEF) with or without type 2 diabetes.

Why this matters

  • DAPA offers a new approach to treating  HFrEF  in patients regardless of type 2 diabetes.

Study design

  • Patients with New York Heart Association (NYHA) class II-IV HF, left ventricular ejection fraction (LVEF)  40%, randomly assigned to DAPA 10 mg daily (n=2373) or placebo (n=2371), all receiving standard medical therapy.
  • Patients with or without type 2 diabetes, N-terminal-prohormone brain natriuretic peptide 600 pg/mL.
  • DAPA-HF funded by AstraZeneca.

Key results

  • The diabetes and no diabetes groups were well matched for age (mean, 67 years), sex, NYHA class, mean LVEF (31%), other laboratory parameters, drug and device treatments.
  • DAPA produced substantial and consistent reductions in death and worsening HF vs placebo, regardless of type 2 diabetes.
  • Primary composite outcome of cardiovascular death/HF hospitalization/urgent HF visit over 24 months:
    • type 2 diabetes: HR, 0.75 (95% CI, 0.63-0.90);
    • no type 2 diabetes: HR, 0.73 (95% CI, 0.60-0.88).
  • Components of outcome:
    • Worsening HF event:
      • type 2 diabetes: HR, 0.77 (95% CI, 0.61-0.95);
      • no type 2 diabetes: HR, 0.62 (95% CI, 0.48-0.80).
    • Cardiovascular death:
      • type 2 diabetes: HR, 0.79 (95% CI, 0.63-1.01);
      • no type 2 diabetes: HR, 0.85 (95% CI, 0.66-1.10).
  • Secondary endpoint: all-cause death.
    • type 2 diabetes: HR, 0.78 (95% CI, 0.63-0.97);
    • no type 2 diabetes: HR, 0.88 (95% CI, 0.70-1.12).
  • Safety/adverse events (AE):
    • type 2 diabetes: any serious AE: DAPA, 41.7% vs placebo, 48.3% (P=.002);
    • no type 2 diabetes: No significant difference.
  • 4.0%-5.4% discontinuation among all groups.

Limitations

  • Results require confirmation.
  • No information on drug sequencing.