Heart failure: efficacy of sacubitril/valsartan across ejection fraction spectrum

  • Solomon SD & al.
  • Circulation
  • 17 Nov 2019

  • curated by Sarfaroj Khan
  • UK Clinical Digest
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  • In patients with heart failure (HF), the therapeutic effects of sacubitril/valsartan vs renin-angiotensin-system (RAS) inhibitor alone varied by left ventricular ejection fraction (LVEF), with greatest therapeutic benefits in those with ejection fraction (EF) below the normal range.
  • These therapeutic benefits appeared to extend to a higher LVEF range in women than men.

Why this matters

  • Findings suggest that patients with EF lower than normal, which includes those with so-called heart failure with mid-range EF or borderline EF would likely benefit from sacubitril/valsartan compared with RAS inhibition.

Study design

  • Study evaluated combined data from PARADIGM-HF (n=8399) and PARAGON-HF (n=4796) trials.
  • All patients with HF were divided into LVEF categories:
    • ≤40%: n=8397;
    • >40 to 50%: n=730; and
    • >50%: n=4067.
  • Time to first CV death and hospitalisation for HF (HHF), its components, all-cause mortality, total HHF and CV death and total HHF were evaluated.
  • Funding: Novartis.

Key results

  • Sacubitril/valsartan was superior to RAS inhibitors in terms of:
    • time to first CV death or HHF (HR, 0.84; 95% CI, 0.78-0.90);
    • CV death (HR, 0.84; 95% CI, 0.76-0.92);
    • HHF (HR, 0.84; 95% CI, 0.77-0.91);
    • all-cause mortality (HR, 0.88; 95% CI, 0.81-0.96);
    • total HHF and CV death (HR, 0.82; 95% CI, 0.75-0.89); and
    • and total HHF (HR, 0.81; 95% CI, 0.73-0.90).
  • Interaction analyses suggested that LVEF was a significant effect modifier of the treatment effect of sacubitril/valsartan for first CV death and HHF (Pinteraction=.02) and therapeutic benefits were greater in patients with EF below the normal range.
  • Effect modification by LVEF on the efficacy of sacubitril/valsartan was similar in both men and women, but the treatment benefits persisted to higher EF in women vs men (Pinteraction=.032).


  • Semi-quantitative estimation of LVEF by site investigators.