Clinical Outcomes in Patients With Acute Decompensated Heart Failure Randomly Assigned to Sacubitril/Valsartan or Enalapril in the PIONEER-HF Trial

Initiation of sacubitril/valsartan shortly after hospitalisation for acutely decompensated heart failure in patients with newly diagnosed (de novo) heart failure: a subgroup analysis of the TRANSITION study

“…PARADIGM‐HF did not provide evidence on the initiation of sacubitril/valsartan in patients hospitalised for acutely decompensated heart failure (ADHF), including those hospitalised with newly diagnosed ( de novo) HFrEF and/or naive to angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs). The PIONEER‐HF study demonstrated a greater reduction in N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) levels and subsequent significant 39% reduction of heart failure (HF) rehospitalisations for sacubitril/valsartan vs. enalapril in patients hospitalised for ADHF …”

In‐hospital initiation of sacubitril/valsartan in acute decompensated heart failure: being in the right place at the right time

“…The low uptake may be partially explained by the more limited experience with sacubitril/valsartan in patients hospitalized for acute decompensated HF (ADHF), patients presenting with severe signs and symptoms of HF, and patients with de novo HF and/or naïve to conventional RAS inhibitors . To address these limitations, PIONEER‐HF was conducted and found that in‐hospital initiation of sacubitril/valsartan vs. enalapril was safe, well‐tolerated, and led to an estimated 45% reduction in HF readmissions within 8 weeks of discharge . In this issue of the Journal, Wachter and colleagues report the primary results of the TRANSITION study, which aimed to assess the tolerability and optimal time point for initiation of sacubitril/valsartan in patients stabilized following admission for ADHF …”

“…Additionally, the study employed an open‐label design with no active comparator arm and the median time from admission to starting sacubitril/valsartan (in‐hospital vs. post‐discharge) was relatively late in both treatment groups (> 7 days) and only differed by several days. The PIONEER‐HF trial showed that early in‐hospital initiation of sacubitril/valsartan vs. enalapril (median time from admission to enrolment of 68 h) resulted in a nearly 45% decreased risk of the serious composite of death from any cause, rehospitalization for HF, left ventricular assist device implantation, or listing for cardiac transplant driven by a reduction in HF readmissions . In addition, at the end of the 8‐week double‐blind treatment phase of the PIONEER‐HF trial, patients in both treatment arms then continued in a 4‐week, open‐label study of sacubitril/valsartan (DeVore A.D., unpublished data presented as a Late‐Breaking Clinical Trial at American College of Cardiology, New Orleans, LA, 2019).…”

Angiotensin–neprilysin inhibition in de novo heart failure – starting off strong

“…As such, a proposed implementation strategy is to consider initiation early in the course of HFrEF, including at the time of index diagnosis, and even prior to exposure to RAAS inhibitors. This up‐front strategy has potential advantages including the ability to influence congestion, ventricular remodelling, lower readmissions and mortality, and improve health status including quality of life earlier in the disease course, but the safety and tolerability of such an approach, particularly in patients who have not previously shown tolerance to ACEI/ARB, has been previously not well characterized.…”