Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study

Abstract

Aims To assess tolerability and optimal time point for initiation of sacubitril/valsartan in patients stabilised after acute heart failure (AHF). Methods and results TRANSITION was a randomised, multicentre, open‐label study comparing two treatment initiation modalities of sacubitril/valsartan. Patients aged ≥ 18 years, hospitalised for AHF were stratified according to pre‐admission use of renin–angiotensin–aldosterone system inhibitors and randomised (n = 1002) after stabilisation to initiate sacubitril/valsartan either ≥ 12‐h pre‐discharge or between Days 1–14 post‐discharge. Starting dose (as per label) was 24/26 mg or 49/51 mg bid with up‐ or down‐titration based on tolerability. The primary endpoint was the proportion of patients attaining 97/103 mg bid target dose after 10 weeks. Median time of first dose of sacubitril/valsartan from the day of discharge was Day –1 and Day +1 in the pre‐discharge group and the post‐discharge group, respectively. Comparable proportions of patients in the pre‐ and post‐discharge initiation groups met the primary endpoint [45.4% vs. 50.7%; risk ratio (RR) 0.90; 95% confidence interval (CI) 0.79–1.02]. The proportion of patients who achieved and maintained for ≥ 2 weeks leading to Week 10, either 49/51 or 97/103 mg bid was 62.1% vs. 68.5% (RR 0.91; 95% CI 0.83–0.99); or any dose was 86.0% vs. 89.6% (RR 0.96; 95% CI 0.92–1.01). Discontinuation due to adverse events occurred in 7.3% vs. 4.9% of patients (RR 1.49; 95% CI 0.90–2.46). Conclusions Initiation of sacubitril/valsartan in a wide range of heart failure with reduced ejection fraction patients stabilised after an AHF event, either in hospital or shortly after discharge, is feasible with about half of the patients achieving target dose within 10 weeks. Clinical Trial Registration: http://ClinicalTrials.gov ID: NCT02661217

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

“…TRANSITION (http://www.clinicaltrials.gov, NCT02661217) was a randomised, multicentre, open‐label study performed in 19 countries and 156 hospitals worldwide. The study design and rationale have been published previously . In brief, the study included male or female subjects aged ≥18 years who were hospitalised for an episode of ADHF ( de novo HFrEF, or due to deterioration of chronic HF), with New York Heart Association (NYHA) class II–IV, blood pressure ≥ 110 mmHg, and left ventricular ejection fraction (LVEF) ≤ 40%.…”

August 2019 at a glance: arrhythmogenic cardiomyopathy, biomarkers of inflammation, insulin treatment, initiation of sacubitril/valsartan, and pharmacy‐based intervention to increase medication adherence

“…It was reached in a similar proportion of patients in the two study groups (45.4% vs. 50.7%). The proportion of patients who achieved and maintained the target dose for ≥2 weeks was also similar …”

Highlights in heart failure

“…4 Ivabradine is indicated in patients in sinus rhythm whose heart rate remains >70 bpm. 4,45 Based on more recent trials, 44,46 it may be considered also in patients hospitalized for acute HF, including also those with new onset HF. 40 Further, 34% of the patients who had a primary event experienced at least one other HF hospitalization and sacubitril/valsartan had a similar efficacy to reduce recurrent events ( Figure 1).…”

“…225 Echocardiography allows an estimate of LV filling pressure and pulmonary artery pressure. 44,46 235,236 Inferior vena cava diameter and jugular venous distension are indexes of venous congestion and right ventricular filling pressure.…”