### Clinical Question
Is the initiation of sacubitril–valsartan therapy more effective than enalapril therapy in reducing the NT-proBNP concentration in patients hospitalized for acute decompensated heart failure with reduced ejection fraction?

### Bottom Line
The initiation of sacubitril–valsartan therapy resulted in a greater reduction in the NT-proBNP concentration than enalapril therapy in patients hospitalized for acute decompensated heart failure with reduced ejection fraction. There were no significant differences between the treatment groups with regard to key safety outcomes.

### Major Points


### Guidelines
Current guidelines do not reflect the results of this trial for in-hospital initiation of sacubitril–valsartan therapy in patients with acute decompensated heart failure.

### Design
Multicenter, randomized, double-blind, active-controlled trial; N=881 patients hospitalized for acute decompensated heart failure.

### Population
Patients aged ≥18 years with heart failure and reduced ejection fraction hospitalized for acute decompensated heart failure.

#### Inclusion Criteria
- Left ventricular ejection fraction ≤40%
- NT-proBNP ≥1600 pg/mL or BNP ≥400 pg/mL
- Signs and symptoms of fluid overload

#### Exclusion Criteria
- Systolic blood pressure <100 mm Hg
- Recent intravenous use of vasodilators or inotropes

#### Baseline Characteristics
- Mean age: 61±14 years
- Male: 72.1%
- Black ethnicity: 35.9%

### Interventions
After hemodynamic stabilization, patients were randomly assigned to:
- Sacubitril–valsartan (target dose, 97 mg/103 mg twice daily)
- Enalapril (target dose, 10 mg twice daily)

### Outcomes
#### Primary Outcomes
- Time-averaged proportional change in NT-proBNP levels from baseline through weeks 4 and 8. Greater reduction seen with sacubitril–valsartan (percent change, −46.7% vs. −25.3%; P<0.001).

#### Secondary Outcomes
- Worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between groups.
- A reduction in high-sensitivity cardiac troponin T concentration with sacubitril–valsartan.

### Criticisms
- The trial protocol required specific conditions for in-hospital initiation of therapy, which may have prolonged hospital stay.
- Loss to follow-up and missing data were present, although multiple imputation analysis accounted for these.

### Funding
The trial was funded by Novartis.

### Further Reading
Original publication in NEJM, "Angiotensin–Neprilysin Inhibition in Acute Decompensated Heart Failure" by Velazquez EJ et al., 2019.