title: Renal dysfunction as a predictor of stroke and systemic embolism in patients with nonvalvular atrial fibrillation: validation of the R(2)CHADS(2) index in the ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation) study cohorts.
abstract: BACKGROUND
  We sought to define the factors associated with the occurrence of stroke and systemic embolism in a large, international atrial fibrillation (AF) trial.
  
  
  RESULTS
  In ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation), 14 264 patients with nonvalvular AF and creatinine clearance ≥30 mL/min were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards modeling was used to identify factors at randomization independently associated with the occurrence of stroke or non-central nervous system embolism based on intention-to-treat analysis. A risk score was developed in ROCKET AF and validated in ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation), an independent AF patient cohort. Over a median follow-up of 1.94 years, 575 patients (4.0%) experienced primary end-point events. Reduced creatinine clearance was a strong, independent predictor of stroke and systemic embolism, second only to prior stroke or transient ischemic attack. Additional factors associated with stroke and systemic embolism included elevated diastolic blood pressure and heart rate, as well as vascular disease of the heart and limbs (C-index 0.635). A model that included creatinine clearance (R(2)CHADS(2)) improved net reclassification index by 6.2% compared with CHA(2)DS(2)VASc (C statistic=0.578) and by 8.2% compared with CHADS(2) (C statistic=0.575). The inclusion of creatinine clearance <60 mL/min and prior stroke or transient ischemic attack in a model with no other covariates led to a C statistic of 0.590.Validation of R(2)CHADS(2) in an external, separate population improved net reclassification index by 17.4% (95% confidence interval, 12.1%-22.5%) relative to CHADS(2).
  
  
  CONCLUSIONS
  In patients with nonvalvular AF at moderate to high risk of stroke, impaired renal function is a potent predictor of stroke and systemic embolism. Stroke risk stratification in patients with AF should include renal function.
  
  
  BACKGROUND
  URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00403767.
authors.affiliation: Division of Cardiology, Duke University Medical Center, Duke Clinical Research Institute, PO Box 17969, Durham, NC 27710, USA. jonathan.piccini@duke.edu
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Piccini
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Stevens
authors.forename: YuChiao
authors.initials: Y
authors.lastname: Chang
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Singer
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lokhnygina
authors.forename: Alan S
authors.initials: AS
authors.lastname: Go
authors.forename: Manesh R
authors.initials: MR
authors.lastname: Patel
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Halperin
authors.forename: Günter
authors.initials: G
authors.lastname: Breithardt
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: Werner
authors.initials: W
authors.lastname: Hacke
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Nessel
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000453:epidemiology; D004311:Double-Blind Method; D004617:Embolism / Q000453:epidemiology / Q000517:prevention & control*; D015951:Factor Xa / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D009025:Morpholines / Q000008:administration & dosage*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012307:Risk Factors; D000069552:Rivaroxaban; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control*; D013876:Thiophenes / Q000008:administration & dosage*; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D014859:Warfarin / Q000008:administration & dosage
chemical_list: D000925:Anticoagulants; D009025:Morpholines; D013876:Thiophenes; D014812:Vitamin K; D014859:Warfarin; D000069552:Rivaroxaban; D015951:Factor Xa