title: Stroke, Major Bleeding, and Mortality Outcomes in Warfarin Users With Atrial Fibrillation and Chronic Kidney Disease: A Meta-Analysis of Observational Studies.
abstract: BACKGROUND
  The use of warfarin in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) can be problematic because of increased bleeding risk. We performed a systematic review and meta-analysis of observational studies that evaluated the use of warfarin in patients with AF and CKD to evaluate the risks of ischemic stroke/thromboembolism, major bleeding, and mortality.
  
  
  METHODS
  PUBMED, EMBASE, CINAHL, ProQuest, and Google Scholar databases were electronically searched through January 12, 2015. Additionally, a manual search was performed for relevant references. Random-effects model was used to estimate the pooled hazard ratio (HR) with 95% CI. CKD was divided into non-end-stage CKD and end-stage CKD (on renal replacement therapy) and separate analyses were performed.
  
  
  RESULTS
  Thirteen publications from 11 cohorts (six retrospective and five prospective) including >48,500 total patients with >11,600 warfarin users were included in the meta-analysis. In patients with AF and non-end-stage CKD, warfarin resulted in a lower risk of ischemic stroke/thromboembolism (HR, 0.70; 95% CI, 0.54-0.89; P = .004) and mortality (HR, 0.65; 95% CI, 0.59-0.72; P < .00001), but had no effect on major bleeding (HR, 1.15; 95% CI, 0.88-1.49; P = .31). In patients with AF and end-stage CKD, warfarin had no effect on the risks of stroke (HR, 1.12; 95% CI, 0.69-1.82; P = .65) and mortality (HR, 0.96; 95% CI, 0.81-1.13; P = .60), but increased the risks of major bleeding (HR, 1.30; 95% CI, 1.08-1.56; P = .005).
  
  
  CONCLUSIONS
  Based on this meta-analysis, the use of warfarin for AF may have an unfavorable risk/benefit ratio in patients with end-stage CKD but not in those with non-end-stage CKD.
authors.affiliation: Department of Medicine, LRGHealthcare, University of New England, Laconia, NH.
authors.forename: Khagendra
authors.initials: K
authors.lastname: Dahal
authors.affiliation: Department of Medicine, LRGHealthcare, University of New England, Laconia, NH.
authors.forename: Sumit
authors.initials: S
authors.lastname: Kunwar
authors.affiliation: Department of Medicine, Miriam Hospital, Alpert Medical School of Brown University, Providence, RI.
authors.forename: Jharendra
authors.initials: J
authors.lastname: Rijal
authors.affiliation: Pat and Jim Calhoun Cardiology Center, University of Connecticut Health Center, Farmington, CT.
authors.forename: Peter
authors.initials: P
authors.lastname: Schulman
authors.affiliation: Pat and Jim Calhoun Cardiology Center, University of Connecticut Health Center, Farmington, CT. Electronic address: jlee@uchc.eu.
authors.forename: Juyong
authors.initials: J
authors.lastname: Lee
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D009026:Mortality; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D017582:Renal Replacement Therapy; D018570:Risk Assessment; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: atrial fibrillation; chronic kidney disease; dialysis; major bleeding; mortality; stroke; warfarin