Velazquez EJ, et al. - Among patients hospitalized for acute decompensated heart failure, researchers tested the effectiveness and safety of initiating sacubitril–valsartan therapy after hemodynamic stabilization in comparison with enalapril therapy. The initiation of sacubitril–valsartan therapy prompted a greater decline in the N-terminal pro–B-type natriuretic peptide (NT-proBNP) concentration than enalapril therapy among patients with heart failure with reduced ejection fraction who were admitted for acute decompensated heart failure. The rate of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema was not significantly different between the sacubitril–valsartan and the enalapril group.

Methods

• Study participants were patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure at 129 sites in the US.
• 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) after hemodynamic stabilization.
• The time-averaged proportional change in the NT-proBNP concentration from baseline through weeks 4 and 8 was the primary efficacy outcome.
• The rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema were key safety outcomes.

Results

• Of the 881 patients randomized, 440 received sacubitril-valsartan and 441 received enalapril.
• The time-averaged reduction of the NT-proBNP concentration in the sacubitril-valsartan group was considerably higher than in the enalapril group.
• The geometric mean ratio of values obtained in weeks 4 and 8 was 0.53 in the sacubitril–valsartan group compared to 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 concentration of NT-proBNP with sacubitril–valsartan than with enalapril was evident from week 1 (ratio of change, 0.76; 95% CI, 0.69 to 0.85).
• The rates of deterioration of renal function, hyperkalemia, symptomatic hypotension, and angioedema were not significantly different between the two groups.