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.
- 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: <26% (n=1143), 26-30% (n=1018), 31-35% (n=1187) and >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.
- 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% (HR, 0.75; 95% CI, 0.59-0.95);
- 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.
- Post hoc analysis.
- LVEF was measured using different methods at different sites.
References
References