title: Digoxin versus placebo, no intervention, or other medical interventions for atrial fibrillation and atrial flutter: a protocol for a systematic review with meta-analysis and Trial Sequential Analysis.
abstract: Atrial fibrillation is the most common arrhythmia of the heart with a prevalence of approximately 2% in the western world. Atrial flutter, another arrhythmia, occurs less often with an incidence of approximately 200,000 new patients per year in the USA. Patients with atrial fibrillation and atrial flutter have an increased risk of death and morbidities. In the management of atrial fibrillation and atrial flutter, it is often necessary to use medical interventions to lower the heart rate. Lowering the heart rate may theoretically prevent the development of heart failure and tachycardia-mediated cardiomyopathy. The evidence on the benefits and harms of digoxin compared with placebo or with other medical interventions is unclear. This protocol for a systematic review aims at identifying the beneficial and harmful effects of digoxin compared with placebo, no intervention, or with other medical interventions for atrial fibrillation and atrial flutter.
  
  
  
  This protocol for a systematic review was conducted following the recommendations of Cochrane and the eight-step assessment procedure suggested by Jakobsen and colleagues. We plan to include all relevant randomised clinical trials comparing digoxin with placebo, no intervention, or with other medical interventions. We plan to search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, Science Citation Index Expanded on Web of Science, and BIOSIS to identify relevant trials. Any eligible trial will be assessed and classified as either at high risk of bias or low risk of bias, and our primary conclusions will be based on trials with low risk of bias. We will perform our meta-analyses of the extracted data using Review Manager 5.3 and Trial Sequential Analysis ver. 0.9.5.5 beta. For both our primary and secondary outcomes, we will create a 'Summary of Findings' table based on GRADE assessments of the quality of the evidence.
  
  
  
  The results of this systematic review have the potential to benefit millions of patients worldwide as well as healthcare economy.
  
  
  
  PROSPERO CRD42016052935.
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. hvg658@alumni.ku.dk.
authors.forename: Naqash J
authors.initials: NJ
authors.lastname: Sethi
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Sanam
authors.initials: S
authors.lastname: Safi
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Joshua
authors.initials: J
authors.lastname: Feinberg
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Emil E
authors.initials: EE
authors.lastname: Nielsen
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.|The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.|The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.|Department of Cardiology, Holbæk Hospital, Holbæk, Denmark.
authors.forename: Janus C
authors.initials: JC
authors.lastname: Jakobsen
mesh_terms: D001281:Atrial Fibrillation / Q000628:therapy*; D001282:Atrial Flutter / Q000188:drug therapy*; D004077:Digoxin / Q000627:therapeutic use*; D006333:Heart Failure / Q000517:prevention & control; D006801:Humans; D010919:Placebos; D000078202:Systematic Reviews as Topic; D015201:Meta-Analysis as Topic
chemical_list: D010919:Placebos; D004077:Digoxin
keywords: Atrial fibrillation; Atrial flutter; Digoxin; Medical therapy; Meta-analysis; Systematic review; Trial Sequential Analysis