title: Net clinical benefit of antithrombotic therapy in patients with atrial fibrillation and chronic kidney disease: a nationwide observational cohort study.
abstract: BACKGROUND
  The balance between stroke reduction and increased bleeding associated with antithrombotic therapy among patients with atrial fibrillation (AF) and chronic kidney disease (CKD) is controversial.
  
  
  OBJECTIVE
  This study assessed the risk associated with CKD in individual CHA₂DS₂-VASc (Congestive heart failure; Hypertension; Age ≥75 years; Diabetes mellitus; previous Stroke, transient ischemic attack, or thromboembolism; Vascular disease; Age 65 to 74 years; Sex category) strata and the net clinical benefit of warfarin in patients with AF and CKD in a nationwide cohort.
  
  
  METHODS
  By individual-level linkage of nationwide Danish registries, we identified all patients discharged with nonvalvular AF from 1997 to 2011. The stroke risk associated with non-end-stage CKD and end-stage CKD (e.g., patients on renal replacement therapy [RRT]) was estimated using Cox regression analyses. The net clinical benefit of warfarin was assessed using 4 endpoints: a composite endpoint of death/hospitalization from stroke/bleeding; a composite endpoint of fatal stroke/fatal bleeding; cardiovascular death; and all-cause death.
  
  
  RESULTS
  From nonvalvular AF patients (n = 154,259), we identified 11,128 patients (7.2%) with non-end-stage CKD and 1,728 (1.1%) receiving RRT. In all CHA₂DS₂-VASc risk groups, RRT was independently associated with a higher risk of stroke/thromboembolism, from a 5.5-fold higher risk in patients with CHA₂DS₂-VASc score = 0 to a 1.6-fold higher risk in patients with CHA₂DS₂-VASc score ≥2. In patients receiving RRT with CHA₂DS₂-VASc score ≥2, warfarin was associated with lower risk of all-cause death (hazard ratio [HR]: 0.85, 95% confidence interval [CI]: 0.72 to 0.99). In non-end-stage CKD patients with CHA₂DS₂-VASc score ≥2, warfarin was associated with a lower risk of a composite outcome of fatal stroke/fatal bleeding (HR: 0.71, 95% CI: 0.57 to 0.88), a lower risk of cardiovascular death (HR: 0.80, 95% CI: 0.74 to 0.88), and a lower risk of all-cause death (HR: 0.64, 95% CI: 0.60 to 0.69).
  
  
  CONCLUSIONS
  CKD is associated with a higher risk of stroke/thromboembolism across stroke risk strata in AF patients. High-risk CKD patients (CHA₂DS₂-VASc ≥2) with AF benefit from warfarin treatment for stroke prevention.
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark.
authors.forename: Anders Nissen
authors.initials: AN
authors.lastname: Bonde
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom.
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.affiliation: Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Rigshospitalet, Denmark.
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Kamper
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark.
authors.forename: Peter Riis
authors.initials: PR
authors.lastname: Hansen
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Lamberts
authors.affiliation: Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Rigshospitalet, Denmark.
authors.forename: Kristine
authors.initials: K
authors.lastname: Hommel
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark.
authors.forename: Morten Lock
authors.initials: ML
authors.lastname: Hansen
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark; The National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.
authors.forename: Gunnar Hilmar
authors.initials: GH
authors.lastname: Gislason
authors.affiliation: Department of Health, Science and Technology, Aalborg University, Aalborg, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark; Department of Cardiology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. Electronic address: anders@nissenbonde.dk.
authors.forename: Jonas Bjerring
authors.initials: JB
authors.lastname: Olesen
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000453:epidemiology; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000453:epidemiology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D012042:Registries; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology* / Q000628:therapy; D017582:Renal Replacement Therapy; D018570:Risk Assessment; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control*; D013923:Thromboembolism / Q000453:epidemiology / Q000517:prevention & control; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D001241:Aspirin
keywords: CHA(2)DS(2)-VASc score; arrhythmia; atrial fibrillation; chronic kidney disease; thromboprophylaxis; warfarin