DAPA-HF: efficacy and safety of dapagliflozin according to LVEF

  • Dewan P & al.
  • Eur J Heart Fail
  • 15 Jun 2020

  • curated by Sarfaroj Khan
  • UK Clinical Digest
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.

Takeaway

  • Left ventricular ejection fraction (LVEF) at baseline was a significant predictor of hospitalisation and mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF).
  • The beneficial effect of sodium-glucose co-transporter 2 inhibitor dapagliflozin on mortality/morbidity outcomes was not modified by LVEF in patients with HFrEF overall, and in those with and without diabetes separately.

Why this matters

  • A key question is whether the benefit of dapagliflozin will extend to patients with HF and mid-range/mildly reduced and preserved ejection fraction, especially in those without diabetes.

Study design

  • DAPA-HF was a phase 3, placebo-controlled trial involving 4744 patients with HF and LVEF ≤40%.
  • This post hoc analysis evaluated whether LVEF at baseline modified the effects of dapagliflozin in DAPA-HF.
  • LVEF categories analysed were: 35% (n=1396).
  • Primary outcome was a composite of a worsening HF (an unplanned hospitalisation for HF or an urgent HF visit requiring intravenous therapy) event or cardiovascular (CV) death.
  • Funding: AstraZeneca.

Key results

  • Mean LVEF was 31.1%.
  • In the overall cohort, each 5% decrease in LVEF was associated with a higher risk of the primary outcome (HR, 1.18; 95% CI, 1.13-1.24; P<.001>
  • The benefit of dapagliflozin over placebo for the primary composite outcome was consistent across the range of LVEF:
    • 26-30% (HR, 0.75; 95% CI, 0.57-0.98);
    • 31-35% (HR, 0.67; 95% CI, 0.51-0.89); and
    • >35% (HR, 0.83; 95% CI, 0.63-1.09; Pinteraction=.762).
  • Similarly, the effect of dapagliflozin on components of the primary outcome was consistent across the range of LVEF:
    • HF hospitalisation/urgent visit for HF (Pinteraction=.161); and
    • CV death (Pinteraction=.974).
  • The safety of dapagliflozin was consistent across the spectrum of LVEF and neither efficacy nor safety was modified by diabetes status.

Limitations

  • Post hoc analysis.
  • LVEF was measured using different methods at different sites.