title: Electrocardiographic assessments and cardiac events after fingolimod first dose - a comprehensive monitoring study.
abstract: BACKGROUND
  First dose observation for cardiac effects is required for fingolimod, but recommendations on the extent vary. This study aims to assess cardiac safety of fingolimod first dose. Individual bradyarrhythmic episodes were evaluated to assess the relevance of continuous electrocardiogram (ECG) monitoring.
  
  
  METHODS
  START is an ongoing open-label, multi-center study. At the time of analysis 3951 patients were enrolled. The primary endpoints are the incidence of bradycardia (heart rate < 45 bpm) and second-/third-degree AV blocks during treatment initiation. The relevance of Holter was assessed by matching ECG findings with the occurrence of clinical symptoms as well as by rigorous analysis of AV blocks with regard to the duration of pauses and the minimal heart rate recorded during AV block.
  
  
  RESULTS
  Thirty-one patients (0.8%) developed bradycardia (<45 bpm), 62 patients (1.6%) had second-degree Mobitz I and/or 2:1 AV blocks with a lowest reading (i.e. mean of ten consecutive beats) of 35 bpm and the longest pause lasting for 2.6 s. No Mobitz II or third-degree AV blocks were observed. Only one patient complained about mild chest discomfort and fatigue. After 1 week, there was no second-/third-degree AV block.
  
  
  CONCLUSIONS
  Continuous Holter ECG monitoring in this large real-life cohort revealed that bradycardia and AV conduction abnormalities were rare, transient and benign. No further unexpected abnormalities were detected. The data presented here give an indication that continuous Holter ECG monitoring does not add clinically relevant value to patients' safety.
  
  
  BACKGROUND
  NCT01585298 ; registered April 23, 2012.
authors.affiliation: Department of Neurology, Cologne General Hospitals, University of Cologne, Cologne, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Limmroth
authors.affiliation: Center of Clinical Neuroscience, University Clinic Carl Gustav Carus Dresden, Dresden, Germany.
authors.forename: Tjalf
authors.initials: T
authors.lastname: Ziemssen
authors.affiliation: NTD Study Group, Neurologische Praxis, Ulm, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lang
authors.affiliation: NeuroMVZ, Stuttgart, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Richter
authors.affiliation: NeuroMVZ, Stuttgart, Germany.
authors.forename: Bert
authors.initials: B
authors.lastname: Wagner
authors.affiliation: Jewish Hospital Berlin, Berlin, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Haas
authors.affiliation: NTD Study Group, Neurologische Gemeinschaftspraxis, Bonn, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Department of Neurology, Cologne General Hospitals, University of Cologne, Cologne, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Gerbershagen
authors.affiliation: Neurologische Gemeinschaftspraxis Kassel und Vellmar, Kassel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Lassek
authors.affiliation: Department of Neurology, University of Muenster, Muenster, Germany.
authors.forename: Luisa
authors.initials: L
authors.lastname: Klotz
authors.affiliation: St. Josefs-Krankenhaus Potsdam-Sanssouci, Potsdam, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Hoffmann
authors.affiliation: St. Josefs-Krankenhaus Potsdam-Sanssouci, Potsdam, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Albert
authors.affiliation: Novartis Pharma GmbH, Nuremberg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schuh
authors.affiliation: Novartis Pharma GmbH, Nuremberg, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Baier-Ebert
authors.affiliation: Novartis Pharma GmbH, Nuremberg, Germany.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Wendt
authors.affiliation: Novartis Pharma GmbH, Nuremberg, Germany.
authors.forename: Heinke
authors.initials: H
authors.lastname: Schieb
authors.affiliation: Novartis Pharma GmbH, Nuremberg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Hoyer
authors.affiliation: Experimental and Clinical Research Center, Charité-Campus Buch, Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
authors.affiliation: Charité Universitaetsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, Berlin, 13353, Germany. wilhelm.haverkamp@charite.de.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Haverkamp
mesh_terms: D000328:Adult; D000368:Aged; D054537:Atrioventricular Block / Q000139:chemically induced* / Q000175:diagnosis; D001919:Bradycardia / Q000139:chemically induced* / Q000175:diagnosis; D015716:Electrocardiography, Ambulatory; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride
keywords: Atrioventricular conduction; Bradycardia; Cardiac effects; Electrocardiogram; Fingolimod; First dose