Rolf Wachter1, Michele Senni2, Jan Belohlavek3, Ewa Straburzynska-Migaj4, Klaus K Witte5, Zhanna Kobalava6, Candida Fonseca7, Eva Goncalvesova8, Yuksel Cavusoglu9, Alberto Fernandez10, Said Chaaban11, Ellen Bøhmer12, Anne-Catherine Pouleur13, Christian Mueller14, Christophe Tribouilloy15, Eva Lonn16, Jehad A L Buraiki17, Jacek Gniot18, Maria Mozheiko19, Malgorzata Lelonek20, Adele Noè21, Heike Schwende21, Weibin Bao22, Dmytro Butylin21, Domingo Pascual-Figal23. 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, UK. 6. Peoples' Friendship University of Russia (RUDN University), Moscow, Russia. 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, Russia. 20. Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland. 21. Novartis Pharma AG, Basel, Switzerland. 22. Novartis Pharmaceuticals, East Hanover, NJ, USA. 23. Cardiology Department, Hospital Universitario Virgen de la Arrixaca, Universidad de Murcia, Murcia, Spain.
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 ofrenin-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.
RCT Entities:
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.
Authors: Fabiana G Marcondes-Braga; Lídia Ana Zytynski Moura; Victor Sarli Issa; Jefferson Luis Vieira; Luis Eduardo Rohde; Marcus Vinícius Simões; Miguel Morita Fernandes-Silva; Salvador Rassi; Silvia Marinho Martins Alves; Denilson Campos de Albuquerque; Dirceu Rodrigues de Almeida; Edimar Alcides Bocchi; Felix José Alvarez Ramires; Fernando Bacal; João Manoel Rossi Neto; Luiz Claudio Danzmann; Marcelo Westerlund Montera; Mucio Tavares de Oliveira Junior; Nadine Clausell; Odilson Marcos Silvestre; Reinaldo Bulgarelli Bestetti; Sabrina Bernadez-Pereira; Aguinaldo F Freitas; Andréia Biolo; Antonio Carlos Pereira Barretto; Antônio José Lagoeiro Jorge; Bruno Biselli; Carlos Eduardo Lucena Montenegro; Edval Gomes Dos Santos Júnior; Estêvão Lanna Figueiredo; Fábio Fernandes; Fabio Serra Silveira; Fernando Antibas Atik; Flávio de Souza Brito; Germano Emílio Conceição Souza; Gustavo Calado de Aguiar Ribeiro; Humberto Villacorta; João David de Souza Neto; Livia Adams Goldraich; Luís Beck-da-Silva; Manoel Fernandes Canesin; Marcelo Imbroinise Bittencourt; Marcely Gimenes Bonatto; Maria da Consolação Vieira Moreira; Mônica Samuel Avila; Otavio Rizzi Coelho Filho; Pedro Vellosa Schwartzmann; Ricardo Mourilhe-Rocha; Sandrigo Mangini; Silvia Moreira Ayub Ferreira; José Albuquerque de Figueiredo Neto; Evandro Tinoco Mesquita Journal: Arq Bras Cardiol Date: 2021-06 Impact factor: 2.000
Authors: David D Berg; Eugene Braunwald; Adam D DeVore; Anuradha Lala; Sean P Pinney; Carol I Duffy; Yared Gurmu; Eric J Velazquez; David A Morrow Journal: JACC Heart Fail Date: 2020-08-12 Impact factor: 12.035