The PIONEER-HF study demonstrated that within eight weeks initiation of Entresto (sacubitril/valsartan) resulted in a significantly greater reduction in NT-proBNP concentration than enalapril therapy before discharge among patients who were stabilized after an event for acute decompensated heart failure (HFrEF). No significant differences were observed between the two groups regarding the pre-specified safety parameters.


Methods

PIONEER-HF was an investigational, multicentre, double-blind, randomised, controlled study in the USA. The study investigated the efficacy and safety of initiating Entresto compared with enalapril before discharge following hospitalisation due to an episode of acute decompensated heart failure.  

  • The primary efficacy outcome was the time-averaged proportional change in NT-proBNP from baseline through weeks 4 and 8.
  • Key safety outcomes were the rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema.

 

The study enrolled patients with heart failure with reduced ejection fraction (HFrEF) who were hospitalized for acute decompensated heart failure and hemodynamically stabilized. 

  • 881 patients with EF ≤ 40% and NT-proBNP ≥ 1600 pg/ml or BNP ≤ 400 pg/ml were randomised to receive Entresto (n=440) or enalapril (n=441) in hospitals in the USA, irrespective of the duration of the diagnosis.
  • All patients were hemodynamically stable (defined as systolic blood pressure ≥ 100 mm Hg for the preceding 6 hours, with no increase in the dose of intravenous diuretics and no use of intravenous vasodilators during the preceding 6 hours, and no use of intravenous inotropes during the preceding 24 hours).
  • Patients were enrolled in the trial after a median time period of 68 hours (interquartile range 48 to 98 hours) from initial arrival at the hospital.

Results

  • Entresto significantly lowered NT-proBNP levels, compared with enalapril, within the geometrical mean of week 4-8 from baseline that was during the hospitalisation (HR = 0.71; 95% CI, 0.63-0.80; p< 0.001). 
  • The greater reduction in the NT-proBNP concentration with Entresto than with enalapril was evident as early as week 1 (ratio of change, 0.76; 95% CI, 0.69 to 0.85). 
  • No significant differences were observed between the two groups regarding the pre-specified safety parameters.

Conclusion

Among patients who were hospitalized for acute decompensated heart failure (HFrEF), initiation of Entresto resulted in a significantly greater reduction in the NT-proBNP concentration than enalapril. There were no significant differences between the two groups with regard to the rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema.


Reference
  1. Velazquez EJ, et al. Angiotensin–Neprilysin Inhibition in Acute Decompensated Heart Failure. N Engl J Med. 2019;380:539-48

 

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SE2204291102 (29 april 2022)
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