Velazquez EJ, et al. - Among patients who were hospitalized for acute decompensated heart failure, researchers ascertained if the initiation of sacubitril–valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) therapy was safe and effective. The initiation of sacubitril–valsartan therapy led to a greater reduction in the NT-proBNP concentration in patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure than enalapril (target dose, 10 mg twice daily) therapy. The rate of deterioration of renal function, hyperkalemia, symptomatic hypotension and angioedema was not significantly different between the two groups.

Methods

• Patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure at 129 sites in the United States were enrolled.
• Patients were randomly assigned to receive sacubitril–valsartan or enalapril after hemodynamic stabilization.
• The time-averaged proportional change in the N-terminal pro–B-type natriuretic peptide (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 randomized patients, 440 received sacubitril–valsartan and 441 received enalapril.
• Findings revealed that the 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 higher 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).
• Between the two groups, the rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly.