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

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. © 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Authors
Wachter R.1 , Senni M.1, 2 , Belohlavek J.3 , Straburzynska-Migaj E.4 , Witte K.K.5 , Kobalava Z. 1, 6 , Fonseca C.1, 7 , Goncalvesova E.1, 8 , Cavusoglu Y.1, 9 , Fernandez A.10 , Chaaban S.1, 11 , Bøhmer E.12 , Pouleur A.-C.1, 13 , Mueller C.14 , Tribouilloy C.1, 15 , Lonn E.1, 16 , A.L. Buraiki J. , Gniot J.1, 18 , Mozheiko M.1, 19 , Lelonek M.1, 20 , Noè A.21 , Schwende H.21 , Bao W.22 , Butylin D.21 , Pascual-Figal D.23 , Gniot J.1, 18 , Mozheiko M.1, 19 , Lelonek M.1, 20 , Dominguez A.R. , Horacek T. , Del Rio E.G. , Kobalava Z. 1, 6 , Mueller C.E. , Cavusoglu Y.1, 9 , Straburzynska-Migaj E.4 , Slanina M. , Vom Dahl J. , Senni M.1, 2 , Ryding A. , Moriarty A. , Robles M.B. , Villota J.N. , Quintana A.G. , Nitschke T. , Manuel Garcia Pinilla J. , Bonet L.A. , Chaaban S.1, 11 , Filali Zaatari S. , Spinar J. , Musial W. , Abdelbaki K. , Belohlavek J.3 , Fehske W. , Bott M.C. , Hoegalmen G. , Leiro M.C. , Ozcan I.T. , Mullens W. , Kryza R. , Al-Ani R. , Loboz-Grudzien K. , Ermoshkina L. , Hojerova S. , Fernandez A.A. , Spinarova L. , Lapp H. , Bulut E. , Almeida F. , Vishnevsky A. , Belicova M. , Pascual D. , Witte K. , Wong K. , Droogne W. , Delforge M. , Peterka M. , Olbrich H.-G. , Carugo S. , Nessler J. , McGill T.H. , Huegl B. , Akin I. , Moreira I. , Baglikov A. , Thambyrajah J. , Hayes C. , Barrionuevo M.R. , Yigit Z. , Kaya H. , Klimsa Z. , Radvan M. , Kadel C. , Landmesser U. , Di Tano G. , Lisik M.B. , Fonseca C.1, 7 , Oliveira L. , Marques I. , Santos L.M. , Lenner E. , Letavay P. , Bueno M.G. , Mota P. , Wong A. , Bailey K. , Foley P. , Hasbani E. , Virani S. , Massih T.A. , Al-Saif S. , Taborsky M. , Kaislerova M. , Motovska Z. , Praha , Logeart D. , Endemann D. , Ferreira D. , Brito D. , Kycina P. , Bollano E. , Basilio E.G. , Rubio L.F. , Aguado M.G. , Schiavi L.B. , Zivano D.F. , Lonn E.1, 16 , Sayed A.E. , Pouleur A.-C.1, 13 , Heyse A. , Schee A. , Polasek R. , Houra M. , Tribouilloy C.1, 15 , Seronde M.F. , Galinier M. , Noutsias M. , Schwimmbeck P. , Voigt I. , Westermann D. , Pulignano G. , Vegsundvaag J. , Alexandre Da Silva Antunes J. , Monteiro P. , Stevlik J. , Goncalvesova E.1, 8 , Hulkoova B. , Juan Castro Fernandez A. , Davies C. , Squire I. , Meyer P. , Sheppard R. , Sahin T. , Sochor K. , De Geeter G. , Wachter R.1 , Schmeisser A. , Weil J. , Soares A.O. , Vasilevna O.B. , Oshurkov A. , Sunderland S.J. , Glover J. , Exequiel T. , Decoulx E. , Meyer S. , Muenzel T. , Frioes F. , Arbolishvili G. , Tokarcikova A. , Karlstrom P. , Carles Trullas Vila J. , Perez G.P. , Sankaranarayanan R. , Nageh T. , Alasia D.C. , Refaat M. , Demirkan B. , Al-Buraiki J. , Karabsheh S. , On Behalf of the TRANSITION Investigators
Publisher
Elsevier Science Publishing Company, Inc.
Language
English
Status
Published
Year
2019
Organizations
  • 1 Clinic and Policlinic for Cardiology, University Hospital Leipzig, and Clinic for Cardiology, University Medicine Göttingen and German Cardiovascular Research Center, Partner Site, Göttingen, Germany
  • 2 Cardiology Division, Cardiovascular Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
  • 3 General Teaching Hospital, Charles University in Prague, Prague, Czech Republic
  • 4 First Department of Cardiology, University of Medical Sciences, Poznan, Poland
  • 5 Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom
  • 6 Peoples' Friendship University of Russia (RUDN University), Moscow, Russian Federation
  • 7 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
  • 8 Odd. Srdcovehozlyhavania a Transplantacie, Bratislava, Slovakia
  • 9 Eskişehir Osmangazi University Medical Faculty, Eskişehir, Turkey
  • 10 Sanatorio Modelo Quilmes, Buenos Aires, Argentina
  • 11 Hammoud Hospital University Medical Center, Saida, Lebanon
  • 12 Innlandet Hospital Trust, Lillehammer, Norway
  • 13 Cardiology Division, Cliniques Universitaires Saint-Luc, Brussels, Belgium
  • 14 University Hospital Basel, University of Basel, Basel, Switzerland
  • 15 Department of Cardiology, Amiens University Hospital, Amiens, France
  • 16 McMaster University and Hamilton Health Sciences, Hamilton, Canada
  • 17 King Faisal Specialist Hospital, Riyadh, Saudi Arabia
  • 18 SP ZOZ Szpital Specjalistyczny, Pulawy, Poland
  • 19 Yaroslavl Regional Hospital of Veterans of Wars, Yaroslavl, Russian Federation
  • 20 Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland
  • 21 Novartis Pharma AG, Basel, Switzerland
  • 22 Novartis Pharmaceuticals, East Hanover, NJ, United States
  • 23 Cardiology Department, Hospital Universitario Virgen de la Arrixaca, Universidad de Murcia, Murcia, Spain
Keywords
Acute decompensated heart failure; Angiotensin receptor–neprilysin inhibitor; Heart failure; Hospitalisation; Sacubitril/valsartan
Date of creation
19.07.2019
Date of change
19.07.2019
Short link
https://repository.rudn.ru/en/records/article/record/38509/
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