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: ClinicalTrials.gov ID: NCT02661217.

1st Department of Cardiology University of Medical Sciences Poznan Poland

Cardiology Department Hospital Universitario Virgen de la Arrixaca Universidad de Murcia Murcia Spain

Cardiology Division Cardiovascular Department Papa Giovanni XXIII Hospital Bergamo Italy

Cardiology Division Cliniques Universitaires Saint Luc Brussels Belgium

Clinic and Policlinic for Cardiology University Hospital Leipzig and Clinic for Cardiology University Medicine Göttingen and German Cardiovascular Research Center Partner Site Göttingen Germany

Department of Cardiology Amiens University Hospital Amiens France

Department of Noninvasive Cardiology Medical University of Lodz Lodz Poland

Eskişehir Osmangazi University Medical Faculty Eskişehir Turkey

General Teaching Hospital Charles University Prague Prague Czech Republic

Hammoud Hospital University Medical Center Saida Lebanon

Heart Failure Unit Internal Medicine Department Hospital de São Francisco Xavier CHLO NOVA Medical School Faculdade de Ciências Médicas Universidade Nova de Lisboa Lisbon Portugal

Innlandet Hospital Trust Lillehammer Norway

King Faisal Specialist Hospital Riyadh Saudi Arabia

Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds Leeds UK

McMaster University and Hamilton Health Sciences Hamilton Canada

Novartis Pharma AG Basel Switzerland

Novartis Pharmaceuticals East Hanover NJ USA

Odd Srdcovehozlyhavania a Transplantacie Bratislava Slovakia

Peoples' Friendship University of Russia Moscow Russia

Sanatorio Modelo Quilmes Buenos Aires Argentina

SP ZOZ Szpital Specjalistyczny Pulawy Poland

University Hospital Basel University of Basel Basel Switzerland

Yaroslavl Regional Hospital of Veterans of Wars Yaroslavl Russia

Eur J Heart Fail. 2019 Aug;21(8):1008-1011. doi: 10.1002/ejhf.1540. PubMed

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ClinicalTrials.gov
NCT02661217