title: Digoxin treatment is associated with increased total and cardiovascular mortality in anticoagulated patients with atrial fibrillation.
abstract: BACKGROUND
  Some evidences suggest that the use of digoxin may be harmful inatrial fibrillation (AF) patients. The aim of the study was to investigate in a "real world" of AF patients receiving vitamin K antagonists (VKAs), the relationship between digoxin use and mortality.
  
  
  METHODS
  Prospective single-center observational study including 815 consecutive non-valvular AF patients treated with VKAs. Total mortality was the primary outcome of the study. We also performed a sub-analysis considering only cardiovascular (CV) deaths. Time in therapeutic range (TTR) was used for anticoagulation quality.
  
  
  RESULTS
  Median follow-up was 33.2months (2460 person-years); 171 (21.0%) patients were taking digoxin. Compared to those without, patients on digoxin were older (p=0.007), with a clinical history of HF (p<0.001) and at higher risk of thromboembolic events (p<0.001). No difference in TTR between the two groups was registered (p=0.598). During the follow-up, 85 deaths occurred: 47 CV and 38 non-CV deaths; 35 deaths occurred in digoxin users (20.6%). A significant increased rate of total mortality was observed in digoxin-treated patients (p<0.001). Multivariable analysis showed that digoxin was associated with total mortality (hazard ratio [HR]: 2.224, p<0.001) and CV death (HR: 4.686, p<0.001). A propensity score-matched analysis confirmed that digoxin was associated with total mortality (HR: 2.073, p=0.0263) and CV death (HR: 4.043, p=0.004).
  
  
  CONCLUSIONS
  In AF patients on good anticoagulation control with VKAs, digoxin use was associated with a higher rate of total and CV mortality.
authors.affiliation: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Umberto I Policlinico of Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Pastori
authors.affiliation: Department of Public Health and Infectious Diseases, Statistics Section, Sapienza University of Rome, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Farcomeni
authors.affiliation: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Umberto I Policlinico of Rome, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Bucci
authors.affiliation: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Umberto I Policlinico of Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cangemi
authors.affiliation: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Umberto I Policlinico of Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ciacci
authors.affiliation: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Umberto I Policlinico of Rome, Italy.
authors.forename: Tommasa
authors.initials: T
authors.lastname: Vicario
authors.affiliation: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Umberto I Policlinico of Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
authors.affiliation: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Umberto I Policlinico of Rome, Italy. Electronic address: pasquale.pignatelli@uniroma1.it.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pignatelli
mesh_terms: D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D002423:Cause of Death / Q000639:trends; D004077:Digoxin / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy / Q000401:mortality*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D057216:Propensity Score; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000401:mortality* / Q000517:prevention & control; D015996:Survival Rate / Q000639:trends
chemical_list: D000889:Anti-Arrhythmia Agents; D000925:Anticoagulants; D004077:Digoxin
keywords: Anticoagulation; Atrial fibrillation; Digoxin; Mortality; Time in therapeutic range