title: On-Treatment Outcomes in Patients With Worsening Renal Function With Rivaroxaban Compared With Warfarin: Insights From ROCKET AF.
abstract: Despite rapid clinical adoption of novel anticoagulants, it is unknown whether outcomes differ among patients with worsening renal function (WRF) taking these new drugs compared with warfarin. We aimed to determine whether the primary efficacy (stroke or systemic embolism) and safety (major bleeding and nonmajor clinically relevant bleeding) end points from the ROCKET AF trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation trial) differed among participants with WRF taking rivaroxaban and those taking warfarin.
  
  
  
  After excluding patients without at least 1 follow-up creatinine measurement (n=1624), we included all remaining patients (n=12 612) randomly assigned to either rivaroxaban or dose-adjusted warfarin. On-treatment WRF (a decrease of >20% from screening creatinine clearance measurement at any time point during the study) was evaluated as a time-dependent covariate in Cox proportional hazards models.
  
  
  
  Baseline characteristics were generally similar between patients with stable renal function (n=9292) and WRF (n=3320). Rates of stroke or systemic embolism, myocardial infarction, and bleeding were also similar, but WRF patients experienced a higher incidence of vascular death versus stable renal function (2.21 versus 1.41 events per 100 patient-years; P=0.026). WRF patients who were randomized to receive rivaroxaban had a reduction in stroke or systemic embolism compared with those taking warfarin (1.54 versus 3.25 events per 100 patient-years) that was not seen in patients with stable renal function who were randomized to receive rivaroxaban (P=0.050 for interaction). There was no difference in major or nonmajor clinically relevant bleeding among WRF patients randomized to warfarin versus rivaroxaban.
  
  
  
  Among patients with on-treatment WRF, rivaroxaban was associated with lower rates of stroke and systemic embolism compared with warfarin, without an increase in the composite bleeding end point.
  
  
  
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767.
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (C.B.F., A.S.H., Y.L., S.M.L., J.P.P., M.R.P.); University of Cincinnati College of Medicine, OH (R.C.B.); Bayer HealthCare Pharmaceuticals, Whippany, NJ (S.D.B); Department of Cardiovascular Medicine, Division of Electrophysiology, University Hospital Münster, Germany (G.B.); Centre for Cardiovascular Science, University of Edinburgh and Royal Infirmary of Edinburgh, UK (K.A.A.F.); Department of Medicine, Stanford University, CA (K.W.M.); Janssen Research and Development, Raritan, NJ (C.C.N.); and Massachusetts General Hospital and Harvard Medical School, Boston (D.E.S.). christopher.fordyce@duke.edu.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Fordyce
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (C.B.F., A.S.H., Y.L., S.M.L., J.P.P., M.R.P.); University of Cincinnati College of Medicine, OH (R.C.B.); Bayer HealthCare Pharmaceuticals, Whippany, NJ (S.D.B); Department of Cardiovascular Medicine, Division of Electrophysiology, University Hospital Münster, Germany (G.B.); Centre for Cardiovascular Science, University of Edinburgh and Royal Infirmary of Edinburgh, UK (K.A.A.F.); Department of Medicine, Stanford University, CA (K.W.M.); Janssen Research and Development, Raritan, NJ (C.C.N.); and Massachusetts General Hospital and Harvard Medical School, Boston (D.E.S.).
authors.forename: Anne S
authors.initials: AS
authors.lastname: Hellkamp
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (C.B.F., A.S.H., Y.L., S.M.L., J.P.P., M.R.P.); University of Cincinnati College of Medicine, OH (R.C.B.); Bayer HealthCare Pharmaceuticals, Whippany, NJ (S.D.B); Department of Cardiovascular Medicine, Division of Electrophysiology, University Hospital Münster, Germany (G.B.); Centre for Cardiovascular Science, University of Edinburgh and Royal Infirmary of Edinburgh, UK (K.A.A.F.); Department of Medicine, Stanford University, CA (K.W.M.); Janssen Research and Development, Raritan, NJ (C.C.N.); and Massachusetts General Hospital and Harvard Medical School, Boston (D.E.S.).
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lokhnygina
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (C.B.F., A.S.H., Y.L., S.M.L., J.P.P., M.R.P.); University of Cincinnati College of Medicine, OH (R.C.B.); Bayer HealthCare Pharmaceuticals, Whippany, NJ (S.D.B); Department of Cardiovascular Medicine, Division of Electrophysiology, University Hospital Münster, Germany (G.B.); Centre for Cardiovascular Science, University of Edinburgh and Royal Infirmary of Edinburgh, UK (K.A.A.F.); Department of Medicine, Stanford University, CA (K.W.M.); Janssen Research and Development, Raritan, NJ (C.C.N.); and Massachusetts General Hospital and Harvard Medical School, Boston (D.E.S.).
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Lindner
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (C.B.F., A.S.H., Y.L., S.M.L., J.P.P., M.R.P.); University of Cincinnati College of Medicine, OH (R.C.B.); Bayer HealthCare Pharmaceuticals, Whippany, NJ (S.D.B); Department of Cardiovascular Medicine, Division of Electrophysiology, University Hospital Münster, Germany (G.B.); Centre for Cardiovascular Science, University of Edinburgh and Royal Infirmary of Edinburgh, UK (K.A.A.F.); Department of Medicine, Stanford University, CA (K.W.M.); Janssen Research and Development, Raritan, NJ (C.C.N.); and Massachusetts General Hospital and Harvard Medical School, Boston (D.E.S.).
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Piccini
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (C.B.F., A.S.H., Y.L., S.M.L., J.P.P., M.R.P.); University of Cincinnati College of Medicine, OH (R.C.B.); Bayer HealthCare Pharmaceuticals, Whippany, NJ (S.D.B); Department of Cardiovascular Medicine, Division of Electrophysiology, University Hospital Münster, Germany (G.B.); Centre for Cardiovascular Science, University of Edinburgh and Royal Infirmary of Edinburgh, UK (K.A.A.F.); Department of Medicine, Stanford University, CA (K.W.M.); Janssen Research and Development, Raritan, NJ (C.C.N.); and Massachusetts General Hospital and Harvard Medical School, Boston (D.E.S.).
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (C.B.F., A.S.H., Y.L., S.M.L., J.P.P., M.R.P.); University of Cincinnati College of Medicine, OH (R.C.B.); Bayer HealthCare Pharmaceuticals, Whippany, NJ (S.D.B); Department of Cardiovascular Medicine, Division of Electrophysiology, University Hospital Münster, Germany (G.B.); Centre for Cardiovascular Science, University of Edinburgh and Royal Infirmary of Edinburgh, UK (K.A.A.F.); Department of Medicine, Stanford University, CA (K.W.M.); Janssen Research and Development, Raritan, NJ (C.C.N.); and Massachusetts General Hospital and Harvard Medical School, Boston (D.E.S.).
authors.forename: Scott D
authors.initials: SD
authors.lastname: Berkowitz
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (C.B.F., A.S.H., Y.L., S.M.L., J.P.P., M.R.P.); University of Cincinnati College of Medicine, OH (R.C.B.); Bayer HealthCare Pharmaceuticals, Whippany, NJ (S.D.B); Department of Cardiovascular Medicine, Division of Electrophysiology, University Hospital Münster, Germany (G.B.); Centre for Cardiovascular Science, University of Edinburgh and Royal Infirmary of Edinburgh, UK (K.A.A.F.); Department of Medicine, Stanford University, CA (K.W.M.); Janssen Research and Development, Raritan, NJ (C.C.N.); and Massachusetts General Hospital and Harvard Medical School, Boston (D.E.S.).
authors.forename: Günter
authors.initials: G
authors.lastname: Breithardt
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (C.B.F., A.S.H., Y.L., S.M.L., J.P.P., M.R.P.); University of Cincinnati College of Medicine, OH (R.C.B.); Bayer HealthCare Pharmaceuticals, Whippany, NJ (S.D.B); Department of Cardiovascular Medicine, Division of Electrophysiology, University Hospital Münster, Germany (G.B.); Centre for Cardiovascular Science, University of Edinburgh and Royal Infirmary of Edinburgh, UK (K.A.A.F.); Department of Medicine, Stanford University, CA (K.W.M.); Janssen Research and Development, Raritan, NJ (C.C.N.); and Massachusetts General Hospital and Harvard Medical School, Boston (D.E.S.).
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (C.B.F., A.S.H., Y.L., S.M.L., J.P.P., M.R.P.); University of Cincinnati College of Medicine, OH (R.C.B.); Bayer HealthCare Pharmaceuticals, Whippany, NJ (S.D.B); Department of Cardiovascular Medicine, Division of Electrophysiology, University Hospital Münster, Germany (G.B.); Centre for Cardiovascular Science, University of Edinburgh and Royal Infirmary of Edinburgh, UK (K.A.A.F.); Department of Medicine, Stanford University, CA (K.W.M.); Janssen Research and Development, Raritan, NJ (C.C.N.); and Massachusetts General Hospital and Harvard Medical School, Boston (D.E.S.).
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (C.B.F., A.S.H., Y.L., S.M.L., J.P.P., M.R.P.); University of Cincinnati College of Medicine, OH (R.C.B.); Bayer HealthCare Pharmaceuticals, Whippany, NJ (S.D.B); Department of Cardiovascular Medicine, Division of Electrophysiology, University Hospital Münster, Germany (G.B.); Centre for Cardiovascular Science, University of Edinburgh and Royal Infirmary of Edinburgh, UK (K.A.A.F.); Department of Medicine, Stanford University, CA (K.W.M.); Janssen Research and Development, Raritan, NJ (C.C.N.); and Massachusetts General Hospital and Harvard Medical School, Boston (D.E.S.).
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Nessel
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (C.B.F., A.S.H., Y.L., S.M.L., J.P.P., M.R.P.); University of Cincinnati College of Medicine, OH (R.C.B.); Bayer HealthCare Pharmaceuticals, Whippany, NJ (S.D.B); Department of Cardiovascular Medicine, Division of Electrophysiology, University Hospital Münster, Germany (G.B.); Centre for Cardiovascular Science, University of Edinburgh and Royal Infirmary of Edinburgh, UK (K.A.A.F.); Department of Medicine, Stanford University, CA (K.W.M.); Janssen Research and Development, Raritan, NJ (C.C.N.); and Massachusetts General Hospital and Harvard Medical School, Boston (D.E.S.).
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Singer
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (C.B.F., A.S.H., Y.L., S.M.L., J.P.P., M.R.P.); University of Cincinnati College of Medicine, OH (R.C.B.); Bayer HealthCare Pharmaceuticals, Whippany, NJ (S.D.B); Department of Cardiovascular Medicine, Division of Electrophysiology, University Hospital Münster, Germany (G.B.); Centre for Cardiovascular Science, University of Edinburgh and Royal Infirmary of Edinburgh, UK (K.A.A.F.); Department of Medicine, Stanford University, CA (K.W.M.); Janssen Research and Development, Raritan, NJ (C.C.N.); and Massachusetts General Hospital and Harvard Medical School, Boston (D.E.S.).
authors.forename: Manesh R
authors.initials: MR
authors.lastname: Patel
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000150:complications; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D004617:Embolism / Q000517:prevention & control; D065427:Factor Xa Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D000069552:Rivaroxaban / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020521:Stroke / Q000517:prevention & control; D019851:Thrombophilia / Q000188:drug therapy / Q000209:etiology; D014859:Warfarin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D065427:Factor Xa Inhibitors; D014859:Warfarin; D000069552:Rivaroxaban; D003404:Creatinine
keywords: anticoagulants; atrial fibrillation; kidney; renal insufficiency