title: Insulin-Requiring Versus Noninsulin-Requiring Diabetes and Thromboembolic Risk in Patients With Atrial Fibrillation: PREFER in AF.
abstract: BACKGROUND
  Diabetes is a known risk predictor for thromboembolic events in patients with atrial fibrillation (AF), but no study has explored the prognostic weight of insulin in this setting.
  
  
  OBJECTIVE
  This study evaluated the differential role of insulin versus no insulin therapy on thromboembolic risk in patients with diabetes and AF.
  
  
  METHODS
  We accessed individual patient data from the prospective, real-world, multicenter, PREFER in AF (European Prevention of thromboembolic events-European Registry in Atrial Fibrillation). We compared the rates of stroke/systemic embolism at 1 year according to diabetes status (no diabetes, diabetes without insulin therapy, diabetes on insulin therapy).
  
  
  RESULTS
  In an overall population of 5,717 patients, 1,288 had diabetes, 22.4% of whom were on insulin. For patients with diabetes who were on insulin, there was a significantly increased risk of stroke/systemic embolism at 1 year versus either no diabetes (5.2% vs. 1.9%; hazard ratio: 2.89; 95% confidence interval: 1.67 to 5.02; p = 0.0002) or diabetes without insulin treatment (5.2% vs. 1.8%; hazard ratio: 2.96; 95% confidence interval: 1.49 to 5.87; p = 0.0019). Notably, rates of stroke/embolism were similar in patients with diabetes not receiving insulin versus patients without diabetes (hazard ratio: 0.97; 95% confidence interval: 0.58 to 1.61; p = 0.90). The selective predictive role of insulin-requiring diabetes was independent of potential confounders, including diabetes duration, and was maintained in various subpopulations, including the subgroup receiving anticoagulant therapy.
  
  
  CONCLUSIONS
  In this cohort of anticoagulated patients with AF, the sole presence of diabetes not requiring insulin did not imply an increased thromboembolic risk. Conversely, insulin-requiring diabetes contributed most, if not exclusively, to the overall increase of thromboembolic risk in AF.
authors.affiliation: Department of Cardiovascular Sciences, Campus Bio-Medico University of Rome, Rome, Italy. Electronic address: g.patti@unicampus.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Patti
authors.affiliation: Daiichi-Sankyo Europe, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Lucerna
authors.affiliation: Department of Cardiovascular Sciences, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cavallari
authors.affiliation: Department of Cardiovascular Sciences, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ricottini
authors.affiliation: G. d'Annunzio University of Chieti, Chieti, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Renda
authors.affiliation: Institute of Informatics, Academy of Sciences of Czech Republic, Prague, Czech Republic.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Pecen
authors.affiliation: Daiichi-Sankyo Italy, Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Romeo
authors.affiliation: Cardiology and Arrhythmology, Georges Pompidou Hospital, René Descartes University, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Le Heuzey
authors.affiliation: Department of Cardiology, University Hospital Ramòn y Cajal, Madrid, Spain.
authors.forename: Josè Luis
authors.initials: JL
authors.lastname: Zamorano
authors.affiliation: Institute of Cardiovascular Sciences, University of Birmingham and Sandwell and West Birmingham Hospitals and University Hospitals Birmingham NHS Trust, Birmingham, United Kingdom; Hospital of the University of Münster, Münster, Germany.
authors.forename: Paulus
authors.initials: P
authors.lastname: Kirchhof
authors.affiliation: G. d'Annunzio University of Chieti, Chieti, Italy; Fondazione G. Monasterio, Pisa, Italy. Electronic address: rdecater@unich.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation; D048909:Diabetes Complications; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D005260:Female; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D013923:Thromboembolism / Q000209:etiology* / Q000517:prevention & control
chemical_list: D007328:Insulin
keywords: CHA(2)DS(2)-VASc score; registry; risk prediction; stroke; systemic embolism