title: Warfarin use and stroke, bleeding and mortality risk in patients with end stage renal disease and atrial fibrillation: a systematic review and meta-analysis.
abstract: Patients with end stage renal disease (ESRD), including stage 5 chronic kidney disease (CKD), hemodialysis (HD) and peritoneal dialysis (PD), are at high risk for stroke-related morbidity, mortality and bleeding. The overall risk/benefit balance of warfarin treatment among patients with ESRD and AF remains unclear.
  
  
  
  We systematically reviewed the associations of warfarin use and stroke outcome, bleeding outcome or mortality in patients with ESRD and AF. We conducted a comprehensive literature search in Feb 2016 using key words related to ESRD, AF and warfarin in PubMed, Embase and Cochrane Library without language restriction. We searched for randomized trials and observational studies that compared the use of warfarin with no treatment, aspirin or direct oral anticoagulants (DOACs), and reported quantitative risk estimates on these outcomes. Paired reviewers screened articles, collected data and performed qualitative assessment using the Cochrane Risk of Bias Assessment Tool for Non-randomized Studies of Interventions. We conducted meta-analyses using the random-effects model with the DerSimonian - Laird estimator and the Knapp-Hartung methods as appropriate.
  
  
  
  We identified 2709 references and included 20 observational cohort studies that examined stroke outcome, bleeding outcome and mortality associated with warfarin use in 56,146 patients with ESRD and AF. The pooled estimates from meta-analysis for the stroke outcome suggested that warfarin use was not associated with all-cause stroke (HR = 0.92, 95 % CI 0.74-1.16) or any stroke (HR = 1.01, 95 % CI 0.81-1.26), or ischemic stroke (HR = 0.80, 95 % CI 0.58-1.11) among patients with ESRD and AF. In contrast, warfarin use was associated with significantly increased risk of all-cause bleeding (HR = 1.21, 95 % CI 1.01-1.44), but not associated with major bleeding (HR = 1.18, 95 % CI 0.82-1.69) or gastrointestinal bleeding (HR = 1.19, 95 % CI 0.81-1.76) or any bleeding (HR = 1.21, 95 % CI 0.99-1.48). There was insufficient evidence to evaluate the association between warfarin use and mortality in this population (pooled risk estimate not calculated due to high heterogeneity). Results on DOACs were inconclusive due to limited relevant studies.
  
  
  
  Given the absence of efficacy and an increased bleeding risk, these findings call into question the use of warfarin for AF treatment among patients with ESRD.
authors: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD, 21205, USA.|Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors: Jingwen
authors: J
authors: Tan
authors: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD, 21205, USA.
authors: Shuiqing
authors: S
authors: Liu
authors: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD, 21205, USA.|Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.|Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.|Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors: Jodi B
authors: JB
authors: Segal
authors: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD, 21205, USA.|Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.|Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors: G Caleb
authors: GC
authors: Alexander
authors: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD, 21205, USA. mara@jhu.edu.|Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. mara@jhu.edu.|Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA. mara@jhu.edu.|Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA. mara@jhu.edu.
authors: Mara
authors: M
authors: McAdams-DeMarco
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects*; D001281:Atrial Fibrillation / Q000150:complications* / Q000401:mortality; D006470:Hemorrhage / Q000453:epidemiology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000401:mortality / Q000628:therapy; D006435:Renal Dialysis; D020521:Stroke / Q000453:epidemiology*; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: Anticoagulants; Atrial fibrillation; End stage renal disease; Warfarin