title: Efficacy and safety of rivaroxaban in patients with diabetes and nonvalvular atrial fibrillation: the Rivaroxaban Once-daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF Trial).
abstract: BACKGROUND
  The prevalence of both atrial fibrillation (AF) and diabetes mellitus (DM) are rising, and these conditions often occur together. Also, DM is an independent risk factor for stroke in patients with AF. We aimed to examine the safety and efficacy of rivaroxaban vs warfarin in patients with nonvalvular AF and DM in a prespecified secondary analysis of the ROCKET AF trial.
  
  
  METHODS
  We stratified the ROCKET AF population by DM status, assessed associations with risk of outcomes by DM status and randomized treatment using Cox proportional hazards models, and tested for interactions between randomized treatments. For efficacy, primary outcomes were stroke (ischemic or hemorrhagic) or non-central nervous system embolism. For safety, the primary outcome was major or nonmajor clinically relevant bleeding.
  
  
  RESULTS
  The 5,695 patients with DM (40%) in ROCKET AF were younger, were more obese, and had more persistent AF, but fewer had previous stroke (the CHADS2 score includes DM and stroke). The relative efficacy of rivaroxaban and warfarin for prevention of stroke and systemic embolism was similar in patients with (1.74 vs 2.14/100 patient-years, hazard ratio [HR] 0.82) and without (2.12 vs 2.32/100 patient-years, HR 0.92) DM (interaction P = .53). The safety of rivaroxaban vs warfarin regarding major bleeding (HRs 1.00 and 1.12 for patients with and without DM, respectively; interaction P = .43), major or nonmajor clinically relevant bleeding (HRs 0.98 and 1.09; interaction P = .17), and intracerebral hemorrhage (HRs 0.62 and 0.72; interaction P = .67) was independent of DM status. Adjusted exploratory analyses suggested 1.3-, 1.5-, and 1.9-fold higher 2-year rates of stroke, vascular mortality, and myocardial infarction in DM patients.
  
  
  CONCLUSIONS
  The relative efficacy and safety of rivaroxaban vs warfarin was similar in patients with and without DM, supporting use of rivaroxaban as an alternative to warfarin in diabetic patients with AF.
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Sameer
authors.initials: S
authors.lastname: Bansilal
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Bloomgarden
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: jonathan.halperin@mssm.edu.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Halperin
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Hellkamp
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lokhnygina
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: Manesh R
authors.initials: MR
authors.lastname: Patel
authors.affiliation: University of Cincinnati College of Medicine, Cincinnati, OH.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.affiliation: Department of Cardiovascular Medicine, Division of Electrophysiology, University Hospital Münster, Münster, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Breithardt
authors.affiliation: Ruprecht-Karls University, Heidelberg, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Hacke
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.affiliation: Janssen Research & Development, Raritan, NJ.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Nessel
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Singer
authors.affiliation: Bayer HealthCare Pharmaceuticals, Whippany, NJ.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Berkowitz
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Piccini
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
mesh_terms: D000284:Administration, Oral; D000368:Aged; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D003920:Diabetes Mellitus / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004617:Embolism / Q000209:etiology / Q000517:prevention & control*; D065427:Factor Xa Inhibitors / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000069552:Rivaroxaban / Q000008:administration & dosage*; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D065427:Factor Xa Inhibitors; D014812:Vitamin K; D000069552:Rivaroxaban