Velazquez EJ, Morrow DA, DeVore AD, et al., for the PIONEER-HF Investigators. Angiotensin–Neprilysin Inhibition in Acute Decompensated Heart Failure. N Engl J Med. 2018 Nov 11 [epub ahead of print].
Pablo Avanzas. Professor of Medicine, Universidad de Oviedo; Consultant in Interventional Cardiology, Hospital Universitario Central de Asturias, Spain
Acute decompensated heart failure accounts for more than 1 million hospitalizations in the United States annually. Whether the initiation of sacubitril–valsartan therapy is safe and effective among patients who are hospitalized for acute decompensated heart failure is unknown. PIONEER-HF 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 time-averaged reduction in the NT-proBNP concentration (primary endpoint) was significantly greater in the sacubitril–valsartan group than in the enalapril group. 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). The rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups.
The results of the PIONEER-HF trial extend the evidence base regarding the use of sacubitril–valsartan to populations for which there had been limited or no data, including patients who are hospitalized for acute decompensated heart failure, patients who have new heart failure, patients who have not been exposed to high doses of guideline-directed medications for heart failure, and patients who are not receiving conventional renin–angiotensin system inhibitors. There was also a reduction in troponin T, and although not powered for clinical endpoints, a reduction in rehospitalization for heart failure was noted over the follow-up period. Side effects including hyperkalemia and hypotension were similar.
As long as acute heart failure patients are medically stable, the PIONEER-HF data support earlier initiation of sacubitril/valsartan, starting them in hospital and continuing long-term.