PIONEER - HF - sacubitril in acute decompensated heart failure

Sacubitril-valsartan is an angiotensin receptor-neprilysin inhibitor that is indicated for the treatment of patients with symptomatic heart failure with reduced ejection fraction

• in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, the use of sacubitril-valsartan resulted in a lower risk of death from cardiovascular causes or hospitalization for heart failure than the use of enalapril in this population (1)
  
  
• enrolled patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure at 129 sites in the United States. After hemodynamic stabilization, patients were randomly assigned to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or enalapril (target dose, 10 mg twice daily). The primary efficacy outcome was the time-averaged proportional change in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration from baseline through weeks 4 and 8. Key safety outcomes were the rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema
  
  
• summary results:
  • of the 881 patients who underwent randomization, 440 were assigned to receive sacubitril-valsartan and 441 to receive enalapril
  • time-averaged reduction in the NT-proBNP concentration was significantly greater in the sacubitril-valsartan group than in the enalapril group; the ratio of the geometric mean of values obtained at weeks 4 and 8 to the baseline value was 0.53 in the sacubitril-valsartan group as compared with 0.75 in the enalapril group (percent change, -46.7% vs. -25.3%; ratio of change with sacubitril-valsartan vs. enalapril, 0.71; 95% confidence interval [CI], 0.63 to 0.81; P<0.001)
  • the greater reduction in the NT-proBNP concentration with sacubitril-valsartan than with enalapril was evident as early as week 1 (ratio of change, 0.76; 95% CI, 0.69 to 0.85)
  • rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups
    
    
• study authors concluded "..Among patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure, the initiation of sacubitril-valsartan therapy led to a greater reduction in the NT-proBNP concentration than enalapril therapy. Rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups.."

Reference:

• McMurray JJ, Packer M, Desai AS, et al. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF). Eur J Heart Fail 2013;15:1062-1073.
• Velazquez EJ et al. Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure.N Engl J Med. 2018 Nov 11. doi: 10.1056/NEJMoa1812851.