Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use
Authors: Papp Zoltán , Agostoni Piergiuseppe , Alvarez Julian , Bettex Dominique , Bouchez Stefan , Brito Dulce , Černý Vladimir , Comin-Colet Josep , Crespo-Leiro Marisa G , Delgado Juan F , Édes Istvan , Eremenko Alexander A , Farmakis Dimitrios , Fedele Francesco , Fonseca Cândida , Fruhwald Sonja , Girardis Massimo , Guarracino Fabio , Harjola Veli-Pekka , Heringlake Matthias , Herpain Antoine , Heunks Leo MA , Husebye Tryggve , Ivancan Višnja , Karason Kristjan , Kaul Sundeep , Kivikko Matti , Kubica Janek , Masip Josep , Matskeplishvili Simon , Mebazaa Alexandre , Nieminen Markku S , Oliva Fabrizio , Papp Julius-Gyula , Parissis John , Parkhomenko Alexander , Põder Pentti , Pölzl Gerhard , Reinecke Alexander , Ricksten Sven-Erik , Riha Hynek , Rudiger Alain , Sarapohja Toni , Schwinger Robert HG , Toller Wolfgang , Tritapepe Luigi , Tschöpe Carsten , Wikström Gerhard , Lewinski Dirk von , Vrtovec Bojan , Pollesello Piero ,   Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary,   Department of Clinical Sciences and Community Health, Centro Cardiologico Monzino, IRCCS, Milan, Italy,   Department of Surgery, School of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain,   Institute of Anaesthesiology, University Hospital of Zurich, Zurich, Switzerland,   Department of Anaesthesiology, University Hospital, Ghent, Belgium,   Cardiology Department, Centro Hospitalar Universitario Lisboa Norte, CCUI, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal,   Department of Anaesthesiology, Perioperative Medicine and Intensive Care, Masaryk Hospital, J.E. Purkinje University, Usti nad Labem, Czech Republic,   Heart Diseases Institute, Hospital Universitari de Bellvitge, Barcelona, Spain,   Complexo Hospitalario Universitario A Coruña (CHUAC), CIBERCV, Instituto de Investigacion Biomedica A Coruña (INIBIC), Universidad de a Coruña (UDC), La Coruña, Spain,   Heart Failure and Transplant Program, Cardiology Department, University Hospital 12 Octubre, Madrid, Spain,   Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary,   Department of Cardiac Intensive Care, Petrovskii National Research Centre of Surgery, Sechenov University, Moscow, Russia,   Department of Cardiology, Medical School, University of Cyprus, Nicosia, Cyprus,   Department of Cardiovascular, Respiratory, Nephrology, Anaesthesiology and Geriatric Sciences, La Sapienza University of Rome, Rome, Italy,   Heart Failure Clinic, São Francisco Xavier Hospital, CHLO, Lisbon, Portugal,   Department of Anaesthesiology and Intensive Care Medicine, Division of Anaesthesiology for Cardiovascular Surgery and Intensive Care Medicine, Medical University of Graz, Graz, Austria,   Struttura Complessa di Anestesia 1, Policlinico di Modena, Modena, Italy,   Dipartimento di Anestesia e Terapie Intensive, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy,   Emergency Medicine, Meilahti Central University Hospital, University of Helsinki, Helsinki, Finland,   Department of Anaesthesiology and Intensive Care Medicine, University of Lübeck, Lübeck, Germany,   Department of Intensive Care, Hôpital Erasme, Brussels, Belgium,   Department of Intensive Care Medicine, Amsterdam UMC, Amsterdam, the Netherlands,   Department of Cardiology, Oslo University Hospital Ullevaal, Oslo, Norway,   Department of Anaesthesiology, Reanimatology and Intensive Care, University Hospital Centre, Zagreb, Croatia,   Departments of Cardiology and Transplantation, Sahlgrenska University Hospital, Gothenburg, Sweden,   Intensive Care Unit, National Health Service, Leeds, UK,   Global Medical Affairs, R&D, Orion Pharma, Espoo, Finland,   Department of Cardiology and Internal Medicine, Nicolaus Copernicus University, Torun, Poland,   Intensive Care Department, Consorci Sanitari Integral, University of Barcelona, Barcelona, Spain,   Lomonosov Moscow State University Medical Centre, Moscow, Russia,   Department of Anaesthesiology and Critical Care Medicine, AP-HP, Saint Louis and Lariboisière University Hospitals, Paris, France,   Sydäntutkimussäätiö, Helsinki, Finland,   Department of Cardiology, Niguarda Ca’Granda Hospital, Milan, Italy,   MTA-SZTE Research Group of Cardiovascular Pharmacology, Hungarian Academy of Sciences, University of Szeged, Szeged, Hungary,   Second Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece,   Emergency Cardiology Department, National Scientific Centre MD Strazhesko Institute of Cardiology, Kiev, Ukraine,   Department of Cardiology, North Estonia Medical Centre, Tallinn, Estonia,   Department of Internal Medicine III, Cardiology and Angiology, Medical University of Innsbruck, Innsbruck, Austria,   Klinik für Innere Medizin III, Kardiologie, Universitätsklinikum Schleswig-Holstein, Kiel, Germany,   Department of Anaesthesiology and Intensive Care, Sahlgrenska University Hospital, Gothenburg, Sweden,   Cardiothoracic Anaesthesiology and Intensive Care, Department of Anaesthesiology and Intensive Care Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic,   Department of Medicine, Spittal Limmattal, Schlieren, Switzerland,   Statistical Services, R&D, Orion Pharma, Espoo, Finland,   Medizinische Klinik II, Klinikum Weiden, Teaching Hospital of University of Regensburg, Weiden, Germany,   Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria,   Anaesthesia and Intensive Care Division, San Camillo-Forlanini Hospital, Rome, Italy,   Department of Cardiology, Campus Virchow Klinikum, Charité – University Medicine Berlin, Berlin, Germany,   Institute of Medical Sciences, Uppsala University, Uppsala, Sweden,   Department of Cardiology, Myokardiale Energetik und Metabolismus Research Unit, Medical University of Graz, Graz, Austria,   Advanced Heart Failure and Transplantation Centre, Department of Cardiology, University Clinical Centre, Ljubljana, Slovenia,   Critical Care Proprietary Products, Orion Pharma, Espoo, Finland
Published: July 2020

Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine. Levosimendan is currently in active clinical evaluation in the US. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and non-cardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, UK and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute heart failure arena in recent times and charts a possible development trajectory for the next 20 years.