Clinical Outcomes in Patients With Acute Decompensated Heart Failure Randomly Assigned to Sacubitril/Valsartan or Enalapril in the PIONEER-HF Trial
Authors: David A. Morrow, Eric J. Velazquez, Adam D. DeVore, Akshay S. Desai, Carol I. Duffy, Andrew P. Ambrosy, Yared Gurmu, Kevin McCague, Ricardo Rocha, Eugene Braunwald
Journal: Circulation (2019)

enalapril ◼ heart failure ◼ hospitalization ◼ valsartan I n outpatients with chronic heart failure (HF) with reduced ejection fraction known to tolerate an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, substitution of the angiotensin-neprilysin inhibitor sacubitril/valsartan reduces the rate of cardiovascular death or HF hospitalization. 1 Accordingly, consensus guidelines recommend the use of sacubitril/valsartan to treat patients with symptomatic HF with reduced ejection fraction. 2Until recently, however, the efficacy and safety of sacubitril/valsartan among patients hospitalized for acute decompensated heart failure (ADHF) was unknown.We have reported the primary results of the randomized double-blind PIONEER-HF trial (Comparison of Sacubitril-Valsartan versus Enalapril on Effect on NT-proBNP in Patients Stabilized from an Acute Heart Failure Episode) demonstrating that, in comparison with enalapril, in patients hemodynamically stabilized during hospitalization for ADHF, sacubitril/ valsartan achieved a greater reduction in N-terminal pro-brain natriuretic peptide concentration, was safe and well-tolerated, and was associated with a significant reduction in the serious composite clinical end point of death, rehospitalization for HF, implantation of a left ventricular assist device, or listing for cardiac transplantation (hazard ratio, 0.54; 95% CI, 0.37-0.79). 3By design, 4 our previously reported analyses of clinical end points relied on investigator-reported data.We undertook an exploratory analysis of the end point of cardiovascular death or rehospitalization for HF to assess the consistency with the results of the pivotal trial in chronic HF. 1 A post hoc adjudication of rehospitalization for HF and cause of death according to standardized definitions 1,5 was performed by the same blinded clinical events committee (CEC) for rigorous confirmation of these end points.In this research letter, we report the results of these additional analyses from PIONEER-HF.PIONEER-HF was an 8-week multicenter, randomized, double-blind, doubledummy, active-controlled trial of in-hospital initiation of sacubitril/valsartan in comparison with enalapril in patients stabilized during hospitalization for ADHF. 4 Eligible patients were to have a left ventricular ejection fraction ≤40% and signs and symptoms of HF along with an N-terminal pro-brain natriuretic peptide concentration ≥1600 pg/mL or brain natriuretic peptide concentration ≥400 pg/mL.Patients were enrolled ≥24 hours and up to 10 days after presentation while still hospitalized and were to be hemodynamically stable using protocol-defined criteria. 4Institutional review boards approved the protocol at all sites.All participants provided written informed consent.We evaluated the cumulative incidence of the adjudicated prespecified exploratory clinical composite end point of death from any cause, rehospitalization for HF, left ventricular assist device implantation, or listing for cardiac transplant, and the composite of cardiovascular death or rehospitalization for HF, as well.