Marco Metra1, John R Teerlink1, Gad Cotter1, Beth A Davison1, G Michael Felker1, Gerasimos Filippatos1, Barry H Greenberg1, Peter S Pang1, Piotr Ponikowski1, Adriaan A Voors1, Kirkwood F Adams1, Stefan D Anker1, Alexandra Arias-Mendoza1, Patricio Avendaño1, Fernando Bacal1, Michael Böhm1, Guillermo Bortman1, John G F Cleland1, Alain Cohen-Solal1, Maria G Crespo-Leiro1, Maria Dorobantu1, Luis E Echeverría1, Roberto Ferrari1, Sorel Goland1, Eva Goncalvesová1, Assen Goudev1, Lars Køber1, Juan Lema-Osores1, Phillip D Levy1, Kenneth McDonald1, Pravin Manga1, Béla Merkely1, Christian Mueller1, Burkert Pieske1, Jose Silva-Cardoso1, Jindřich Špinar1, Iain Squire1, Janina Stępińska1, Walter Van Mieghem1, Dirk von Lewinski1, Gerhard Wikström1, Mehmet B Yilmaz1, Nicole Hagner1, Thomas Holbro1, Tsushung A Hua1, Shalini V Sabarwal1, Thomas Severin1, Peter Szecsödy1, Claudio Gimpelewicz1. 1. From Cardiology, Department of Medical and Surgical Specialties, Radiologic Sciences, and Public Health, University of Brescia, Brescia (M.M.), Centro Cardiologico Universitario di Ferrara, University of Ferrara, Ferrara (R.F.), and Maria Cecilia Hospital, GVM Care and Research, Cotignola (R.F.) - all in Italy; the Section of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine, University of California, San Francisco, San Francisco (J.R.T.), and the Division of Cardiology, University of California, San Diego, La Jolla (B.H.G.) - all in California; Momentum Research (G.C., B.A.D.) and the Division of Cardiology, Duke University School of Medicine (G.M.F.), Durham, and the University of North Carolina, Chapel Hill (K.F.A.) - all in North Carolina; the School of Medicine, University of Cyprus, Nicosia, Cyprus (G.F.); the School of Medicine, National and Kapodistrian University of Athens, Athens (G.F.); the Department of Emergency Medicine, Indiana University School of Medicine, and the Regenstrief Institute, Indianapolis (P.S.P.); the Department of Heart Diseases, Medical University, Military Hospital, Wrocław (P.P.), and Instytut Kardiologii, Warsaw (J.S.) - both in Poland; University of Groningen, Groningen, the Netherlands (A.A.V.); the Department of Internal Medicine and Cardiology, German Center for Cardiovascular Research partner site Berlin (S.D.A., B.P.), and Berlin Institute of Health Center for Regenerative Therapies (S.D.A.), Charité Universitätsmedizin Berlin-Campus Virchow Klinikum, Berlin, and Saarland University, Universitätsklinikum des Saarlandes Homburg, Homburg (M.B.) - all in Germany; the Coronary Care and Emergency Department, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City (A.A.-M.); Hospital Clínico de la Fuerza Aérea de Chile, Las Condes, Chile (P.A.); the Heart Transplantation Department, Heart Institute (InCor), University of São Paulo, and Hospital Israelita Albert Einstein, São Paulo (F.B.); Sanatorio de la Trinidad Mitre, Buenos Aires (G.B.); the Robertson Centre for Biostatistics and Clinical Trials, University of Glasgow, Glasgow (J.G.F.C.), National Heart and Lung Institute, Imperial College, London (J.G.F.C.), and the Department of Cardiovascular Sciences, University of Leicester, and National Institute for Health Research Biomedical Research Centre, Glenfield Hospital, Leicester (I.S.) - all in the United Kingdom; Cardiology Department, Hôpital Lariboisière and Université de Paris, Paris (A.C.-S.); Complejo Hospitalario Universitario A Coruña, Universidade da Coruña, Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, La Coruña, Spain (M.G.C.-L.); Carol Davila University of Medicine and Pharmacy, Bucharest, Romania (M.D.); Heart Failure and Heart Transplant Clinic, Fundación Cardiovascular de Colombia, Floridablanca, Colombia (L.E.E.); Heart Institute, Kaplan Medical Center, Rehovot, Hebrew University, Jerusalem (S.G.); National Cardiovascular Institute, Bratislava, Slovakia (E.G.); Medical University of Sofia, Tzaritza Ioanna University Hospital, Sofia, Bulgaria (A.G.); the Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen (L.K.); Internal Medicine-Cardiology, Internal Medicine Department, Hospital Nacional Arzobispo Loayza, Lima, Peru (J.L.-O.); Wayne State University School of Medicine and Cardiovascular Research Institute, Detroit (P.D.L.); the School of Medicine and Medical Sciences and St. Vincent's University Hospital, University College Dublin, Dublin (K.M.); the Department of Internal Medicine, University of Witwatersrand, Johannesburg (P.M.); Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); the Department of Cardiology and Cardiovascular Research Institute Basel, University Hospital Basel, University of Basel (C.M.), and Novartis Pharma (T.H., T.S., P.S., C.G.), Basel, Switzerland; CINTESIS, Porto University Medical School, São João Medical Center, Porto, Portugal (J.S.-C.); University Hospital Brno and Medical Faculty Masaryk University, Brno, Czech Republic (J.Š.); University Hasselt, Hasselt, Belgium (W.V.M.); the Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria (D.L.); the Institute of Medical Sciences, Uppsala University, Uppsala University Hospital, Uppsala, Sweden (G.W.); Dokuz Eylül University, Faculty of Medicine, Department of Cardiology, Izmir, Turkey (M.B.Y.); and Novartis Pharmaceuticals, East Hanover, NJ (N.H., T.H., T.A.H., S.V.S.).
Abstract
BACKGROUND:Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODS: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS:A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P = 0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P = 0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS: In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days thanplacebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.).
RCT Entities:
BACKGROUND:Serelaxin is a recombinant form of humanrelaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODS: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS: A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P = 0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P = 0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS: In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.).
Authors: Nikola Kozhuharov; Assen Goudev; Dayana Flores; Micha T Maeder; Joan Walter; Samyut Shrestha; Danielle Menosi Gualandro; Mucio Tavares de Oliveira Junior; Zaid Sabti; Beat Müller; Markus Noveanu; Thenral Socrates; Ronny Ziller; Antoni Bayés-Genís; Alessandro Sionis; Patrick Simon; Eleni Michou; Samuel Gujer; Tommaso Gori; Philip Wenzel; Otmar Pfister; David Conen; Ioannis Kapos; Richard Kobza; Hans Rickli; Tobias Breidthardt; Thomas Münzel; Paul Erne; Christian Mueller; Nisha Arenja Journal: JAMA Date: 2019-12-17 Impact factor: 56.272
Authors: Soo Ghee Yeoh; Jia Siang Sum; Jing Yi Lai; W Y Haniff W Isa; Theam Soon Lim Journal: J Cardiovasc Transl Res Date: 2021-08-31 Impact factor: 3.216
Authors: Òscar Miró; Xavier Rossello; Elke Platz; Josep Masip; Danielle M Gualandro; W Frank Peacock; Susanna Price; Louise Cullen; Salvatore DiSomma; Mucio Tavares de Oliveira; John Jv McMurray; Francisco J Martín-Sánchez; Alan S Maisel; Christiaan Vrints; Martin R Cowie; Héctor Bueno; Alexandre Mebazaa; Christian Mueller Journal: Eur Heart J Acute Cardiovasc Care Date: 2020-08