Angiotensin-Neprilysin Inhibition After Acute Decompensated HF

Study Questions:

What are the changes in N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels in patients switching from taking enalapril (titrated to target dose, 10 mg twice daily) to sacubitril/valsartan? Are there any differences in outcomes for patients randomized to receive in-hospital initiation of sacubitril/valsartan versus in-hospital initiation of enalapril who later switched to taking sacubitril/valsartan?


The study authors conducted a secondary analysis of data from the PIONEER-HF trial, which was a multicenter, randomized, double-blind, active-controlled trial that compared the in-hospital initiation of sacubitril/valsartan versus enalapril (titrated to target dose, 10 mg twice daily) for 8 weeks among patients admitted for acute decompensated heart failure (ADHF) with reduced ejection fraction and hemodynamic stability. All patients were to continue in a 4-week, open-label study of sacubitril/valsartan; of 881 patients enrolled in the PIONEER-HF trial, 832 (94%) continued in the open-label study. The main outcome measured by these investigators included: a) changes in NT-proBNP levels from week 8 to 12, as well as b) the exploratory composite of HF rehospitalization or cardiovascular death from randomization through week 12.


Of 881 participants, 27.7% (n = 226) were women, 58.5% (n = 487) were white, 35.7% (n = 297) were black, 1.8% (n = 15) were Asian, and 8.8% (n = 73) were of Hispanic ethnicity; the mean (standard deviation) age was 61 ± 14 years. For patients who continued to take sacubitril/valsartan, NT-proBNP levels declined −17.2% (95% confidence interval [CI], −3.2 to −29.1) from week 8 to 12. The NT-proBNP levels declined to a greater extent for those switching from taking enalapril to sacubitril/valsartan after the week 8 visit (−37.4%; 95% CI, −28.1 to −45.6; p < 0.001; comparing changes in two groups). Over the entire 12 weeks of follow-up, patients who had received sacubitril/valsartan initially in the hospital had a lower incidence of HF rehospitalization or cardiovascular death than those who started to take enalapril in the hospital and then had a delayed initiation of sacubitril/valsartan 8 weeks later (13.0% vs. 18.1%; HR, 0.69; 95% CI, 0.49-0.97; p = 0.03). Among this population, sacubitril-valsartan was well tolerated during in-hospital initiation and during the open-label extension study.


The study authors concluded that switching patients’ treatment from enalapril to sacubitril/valsartan at 8 weeks after randomization led to a further 37% reduction in NT-proBNP levels in patients with heart failure with reduced ejection fraction and a recent hospitalization for ADHF.


Although this is a limited duration, open-label study, the early, observed improvement in post-discharge outcomes suggests that early in-hospital initiation of sacubitril/valsartan in stabilized patients with ADHF is desirable. More data are needed to determine the benefits of ‘door-to-sacubitril/valsartan’ time.

Clinical Topics: Anticoagulation Management, Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Aminobutyrates, Angiotensins, Biological Markers, Enalapril, Heart Failure, Natriuretic Peptide, Brain, Neprilysin, Patient Discharge, Peptide Fragments, Stroke Volume, Tetrazoles, Treatment Outcome

< Back to Listings