• Marco Metra, John R Teerlink, Gad Cotter, Beth A Davison, G Michael Felker, Gerasimos Filippatos, Barry H Greenberg, Peter S Pang, Piotr Ponikowski, Adriaan A Voors, Kirkwood F Adams, Stefan D Anker, Alexandra Arias-Mendoza, Patricio Avendaño, Fernando Bacal, Michael Böhm, Guillermo Bortman, Cleland John G F JGF From Cardiology, Department of Medical and Surgical Specialties, Radiologic Sciences, and Public Health, University of Brescia, Brescia (M.M.), Centr, Alain Cohen-Solal, Maria G Crespo-Leiro, Maria Dorobantu, Luis E Echeverría, Roberto Ferrari, Sorel Goland, Eva Goncalvesová, Assen Goudev, Lars Køber, Juan Lema-Osores, Phillip D Levy, Kenneth McDonald, Pravin Manga, Béla Merkely, Christian Mueller, Burkert Pieske, Jose Silva-Cardoso, Jindřich Špinar, Iain Squire, Janina Stępińska, Walter Van Mieghem, Dirk von Lewinski, Gerhard Wikström, Mehmet B Yilmaz, Nicole Hagner, Thomas Holbro, Tsushung A Hua, Shalini V Sabarwal, Thomas Severin, Peter Szecsödy, Claudio Gimpelewicz, and RELAX-AHF-2 Committees Investigators.
• 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.).
• N. Engl. J. Med. 2019 Aug 22; 381 (8): 716-726.

BackgroundSerelaxin 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.MethodsIn 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.ResultsA 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.ConclusionsIn 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.).Copyright © 2019 Massachusetts Medical Society.

31 keywords...

hide…