METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.