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Invited Commentary
December 11, 2019

Early Implementation of Sacubitril/Valsartan for Patients With Heart Failure

Author Affiliations
  • 1Northwestern University Feinberg School of Medicine, Chicago, Illinois
JAMA Cardiol. 2020;5(2):207-208. doi:10.1001/jamacardio.2019.4822

All the past we leave behind…Pioneers, O Pioneers!

Walt Whitman, Leaves of Grass, 18671

In this issue of JAMA Cardiology, DeVore and colleagues2 provide definitive evidence on the question of the appropriate timing of initiation of the angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan (S/V) during hospitalization for acute decompensated heart failure (ADHF). This study presents the results of the 4 week open-label extension period of the Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-pro-BNP in Patients Stabilized From an Acute Heart Failure Episode (PIONEER-HF) clinical trial, which was an 8-week multicenter, randomized, double-blind, double-dummy, active-controlled trial of in-hospital initiation of S/V compared with enalapril in patients stabilized during hospitalization for ADHF,3 Eligible PIONEER-HF patients had ADHF with a left ventricular ejection fraction of 40% or less along with an N-terminal pro–brain natriuretic peptide (NT-proBNP) concentration of 1600 pg/mL or more or a BNP concentration of 400 pg/mL or more. Patients were enrolled at 24 hours or later and up to 10 days after presentation while still hospitalized and were to be hemodynamically stable (notably, systolic blood pressure >100 mm Hg, not taking inotropic agents for 24 hours, and no increase in intravenous diuretics). Patients taking S/V had a greater reduction in NT-proBNP levels at 8 weeks and fewer clinical events, including rehospitalization for heart failure (HF), compared with enalapril. In a follow-up article,4 clinical events were adjudicated post hoc and the findings again supported favorable associations of S/V with outcomes. In this article,2 DeVore and colleagues report an additional 4 weeks of follow-up in an open-label extension (weeks 8-12), during which all patients were switched to receiving S/V at week 8. The results demonstrated a 37% reduction in NT-proBNP levels with S/V, and among patients converted from taking enalapril to S/V at week 8, there was a marked acceleration associated with that decline. Perhaps most notably, there were fewer events among the arm in which S/V was initiated earlier in the inpatient HF hospitalization course compared with those whose treatment was initiated 2 months posthospitalization (week 8).

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