Combination of sacubitril/valsartan outweighs valsartan alone in worsening heart failure

New research revealed that a combination of sacubitril/valsartan in heart failure patients with more than 40% of ejection fraction and stabilized after worsening heart failure had a greater reduction in plasma NT-proBNP levels and anticipated clinical benefit compared with valsartan alone. The trial results were published in the Journal of the American College of Cardiology. 

In patients with chronic heart failure (HF) and a modestly decreased or maintained ejection fraction (EF), U.S. guidelines advise using sacubitril/valsartan. Sacubitril/valsartan (Sac/Val) was found to be more effective than valsartan (Val) in treating patients with heart failure (HF) and an ejection fraction (EF) ≥45%, according to the PARAGON-HF trial. However, noticeable benefits were seen in patients with mildly reduced EF or heart failure with preserved ejection (HFpEF) with an EF below normal (≤60%). As there is uncertainty about whether the initiation is safe and effective in EF >40% after a worsening heart failure (WHF) event, researchers conducted a PARAGLIDE-HF trial to assess the efficacy, safety, and tolerability of Sac/Val vs Val in a diverse population of patients with EF >40% and a recent worsening heart failure (WHF) event. 

PARAGLIDE-HF is a double-blind, randomized controlled trial of sacubitril/valsartan vs valsartan in patients with EF >40% enrolled within 30 days of a WHF event. The primary endpoint was a time-averaged proportional change in amino-terminal pro–B-type natriuretic peptide (NT-proBNP) from baseline through Weeks 4 and 8. Assessing the cardiovascular death, HF hospitalizations urgent HF visits, and change in NT-proBNP were the secondary hierarchical outcome (win ratio).  

Key findings: 

• Out of 466 patients, there were 233 in the sacubitril/valsartan group and 233 were in the valsartan group.
• The sacubitril/valsartan group showed a greater time-averaged reduction in the NT-proBNP. 
• There was an insignificant favor of the hierarchical outcome in the sacubitril/valsartan group.
• Worsening of renal function was reduced in the Sacubitril/valsartan group but increased symptomatic hypotension. 
• The hugely evident difference in the treatment effect was seen in the subgroup with EF ≤60% for NT-proBNP change and the hierarchical outcome (win ratio: 1.46). 

Thus, treatment with Sac/Val resulted in a larger decrease in NT-proBNP than treatment with Val through 8 weeks across a heterogeneous cohort of patients with EF >40% stable after a recent episode of WHF. 

Further reading: Robert J. Mentz, et al. Angiotensin-Neprilysin Inhibition in Patients With Mildly Reduced or Preserved Ejection Fraction and Worsening Heart Failure. 10.1016/j.jacc.2023.04.019