title: Efficacy and safety of vitamin K-antagonists (VKA) for atrial fibrillation in non-dialysis dependent chronic kidney disease.
abstract: BACKGROUND
  Essential information regarding efficacy and safety of vitamin K-antagonists (VKA) treatment for atrial fibrillation (AF) in non-dialysis dependent chronic kidney disease (CKD) is still lacking in current literature. The aim of our study was to compare the risks of stroke or transient ischemic attack (TIA) and major bleeds between patients without CKD (eGFR >60 ml/min), and those with moderate (eGFR 30-60 ml/min), or severe non-dialysis dependent CKD (eGFR <30 ml/min).
  
  
  METHODS
  We included 300 patients without CKD, 294 with moderate, and 130 with severe non-dialysis dependent CKD, who were matched for age and sex. Uni- and multivariate Cox regression analyses were performed reporting hazard ratios (HRs) for the endpoint of stroke or TIA and the endpoint of major bleeds as crude values and adjusted for comorbidity and platelet-inhibitor use.
  
  
  RESULTS
  Overall, 6.2% (45/724, 1.7/100 patient years) of patients developed stroke or TIA and 15.6% (113/724, 4.8/100 patient years) a major bleeding event. Patients with severe CKD were at high risk of stroke or TIA and major bleeds during VKA treatment compared with those without renal impairment, HR 2.75 (95%CI 1.25-6.05) and 1.66 (95%CI 0.97-2.86), or with moderate CKD, HR 3.93(1.71-9.00) and 1.86 (95%CI 1.08-3.21), respectively. These risks were similar for patients without and with moderate CKD. Importantly, both less time spent within therapeutic range and high INR-variability were associated with increased risks of stroke or TIA and major bleeds in severe CKD patients.
  
  
  CONCLUSIONS
  VKA treatment for AF in patients with severe CKD has a poor safety and efficacy profile, likely related to suboptimal anticoagulation control. Our study findings stress the need for better tailored individualised anticoagulant treatment approaches for patients with AF and severe CKD.
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Judith
authors.initials: J
authors.lastname: Kooiman
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory of Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Nienke
authors.initials: N
authors.lastname: van Rein
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Spaans
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Koen A J
authors.initials: KA
authors.lastname: van Beers
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jonna R
authors.initials: JR
authors.lastname: Bank
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Wilke R
authors.initials: WR
authors.lastname: van de Peppel
authors.affiliation: Department of Internal Medicine, Rijnland Hospital, Leiderdorp, The Netherlands.
authors.forename: Antonio Iglesias
authors.initials: AI
authors.lastname: del Sol
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Cannegieter
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
authors.affiliation: Haemostasis, Thrombosis, and Vascular Biology Unit, 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 Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Frederikus A
authors.initials: FA
authors.lastname: Klok
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Menno V
authors.initials: MV
authors.lastname: Huisman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D002546:Ischemic Attack, Transient / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D018570:Risk Assessment / Q000706:statistics & numerical data; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K