Rationale and design of TRANSITION: a randomized trial of pre‐discharge vs. post‐discharge initiation of sacubitril/valsartan

摘要

Aims The prognosis after hospitalization for acute decompensated heart failure (ADHF) remains poor, especially 30?days post‐discharge. Evidence‐based medications with prognostic impact administered at discharge improve survival and hospital readmission, but robust studies comparing pre‐discharge with post‐discharge initiation are rare. The PARADIGM‐HF trial established sacubitril/valsartan as a new evidence‐based therapy in patients with heart failure (HF) and reduced left ventricular ejection fraction (40%) (rEF). In common with other landmark studies, it enrolled patients who were ambulatory at the time of inclusion. In addition, there is also still limited knowledge of initiation and up‐titration of sacubitril/valsartan in ACEi/ARB‐ na?ve patients and in de novo HF with rEF patients. Methods and results TRANSITION is a multicentre, open‐label study in which ~1000 adults hospitalized for ADHF with rEF are randomized to start sacubitril/valsartan in a pre‐discharge arm (initiated ≥24?h after haemodynamic stabilization) or a post‐discharge arm (initiated within Days?1–14 after discharge). The protocol allows investigators to select the appropriate starting dose and dose adjustments according to clinical circumstances. Over a 10?week treatment period, the primary and secondary objectives assess the feasibility and safety of starting sacubitril/valsartan in‐hospital, early after haemodynamic stabilization. Exploratory objectives also include assessment of HF signs and symptoms, readmissions, N‐terminal pro‐B‐type natriuretic peptide and high‐sensitivity troponin T levels, and health resource utilization parameters. Conclusions TRANSITION will provide new evidence about initiating sacubitril/valsartan following hospitalization for ADHF, occurring either as de novo ADHF or as deterioration of chronic HF, and in patients with or without prior ACEI/ARB therapy. The results of TRANSITION will thus be highly relevant to the management of patients hospitalized for ADHF with rEF.