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Angiotensin-Neprilysin Inhibition in Patients With Mildly Reduced or Preserved Ejection Fraction and Worsening

Robert J Mentz1, Jonathan H Ward2, Adrian F Hernandez1

  • 1Duke Clinical Research Institute, Durham, North Carolina, USA.

Journal of the American College of Cardiology
|May 22, 2023
PubMed

Insights

Sacubitril/valsartan demonstrated greater NT-proBNP reduction in heart failure patients (EF >40%) post-worsening event, showing clinical benefits despite increased hypotension. This study provides key insights into heart failure management.

Area of Science:

  • Cardiology
  • Pharmacology
  • Clinical Trials

Background:

  • U.S. guidelines suggest sacubitril/valsartan for chronic heart failure (HF) with mildly reduced or preserved ejection fraction (EF).
  • The safety and efficacy of initiating sacubitril/valsartan in patients with EF >40% following a worsening heart failure (WHF) event remain uncertain.

Purpose of the Study:

  • To evaluate the effectiveness of sacubitril/valsartan compared to valsartan in patients with EF >40% after a recent WHF event.
  • To assess the impact on NT-proBNP levels and a composite hierarchical outcome including cardiovascular death, HF hospitalizations, and urgent HF visits.

Main Methods:

  • The PARAGLIDE-HF trial was a double-blind, randomized controlled study.
  • Patients with EF >40% were enrolled within 30 days of a WHF event and randomized to sacubitril/valsartan or valsartan.
  • The primary endpoint was the time-averaged proportional change in NT-proBNP; a secondary hierarchical outcome was analyzed using a win ratio.

Main Results:

  • Sacubitril/valsartan showed a significantly greater reduction in NT-proBNP compared to valsartan (P=0.049).
  • The hierarchical outcome favored sacubitril/valsartan but did not reach statistical significance (P=0.16).
  • Sacubitril/valsartan reduced worsening renal function but increased symptomatic hypotension; a larger treatment effect was observed in patients with EF ≤60%.

Conclusions:

  • In stabilized patients with EF >40% post-WHF, sacubitril/valsartan achieved greater NT-proBNP reduction and showed clinical benefits versus valsartan.
  • Despite increased symptomatic hypotension, sacubitril/valsartan offers a potential therapeutic option for this patient population.
  • Further research may explore optimal patient selection, particularly for those with EF ≤60%.
Abstract

Keywords:
HFmrEFacute decompensated HFpEFclinical outcomesnatriuretic peptidessacubitril/valsartan

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