Arrhythmias and Conduction Disturbances
Meta-Analysis of Anticoagulation Use, Stroke, Thromboembolism, Bleeding, and Mortality in Patients With Atrial Fibrillation on Dialysis

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Atrial fibrillation (AF) is common in patients on dialysis. Although randomized trials of anticoagulation for AF have demonstrated striking reductions in stroke, these trials did not recruit patients on dialysis. We thus undertook this systematic review and meta-analysis of observational studies including patients with AF on dialysis that reported associations of anticoagulation use. Twenty studies involving 529,741 subjects and 31,321 patients with AF on dialysis were identified. Anticoagulation was associated with a 45% (95% CI 13% to 88%) increased risk of any stroke, reflecting a nonsignificant 13% (95% CI −4% to 34%) increased ischemic stroke risk and 38% (95% CI 3% to 85%) increased hemorrhagic stroke risk. There was also a 44% (95% CI 38% to 56%) lower risk of any thromboembolism, and a 31% (95% CI 12% to 53%) increased risk of any bleeding but no clear association with cardiovascular death (relative risk 0.99, 95% CI 0.86 to 1.15) or all-cause mortality (relative risk 0.97, 95% CI 0.90 to 1.04). Incident event rates were similar or worse in patients on anticoagulation. In conclusion, these observational analyses provide little supporting evidence of benefit, and instead suggest harm, from anticoagulation in patients on dialysis with AF. These results raise the possibility that the effects of anticoagulation in patients with AF on dialysis may not be similar to the clear benefit of anticoagulation seen in patients with AF without end-stage renal disease. Randomized trials are required to definitively evaluate the safety and efficacy of anticoagulation for AF in the dialysis setting.

Section snippets

Methods

Full details of the methods are presented in the Appendix. In brief, we performed a systematic search of observational studies in MEDLINE and EMBASE databases up to June 2015. Eligible studies included patients with AF on dialysis reporting outcome data according to vitamin K antagonist use (either measures of relative risk [RR] for the association between anticoagulation use and outcomes) or incident event rates according to anticoagulation use. We sought to include patients on either

Results

The systematic search of electronic databases identified 1,884 studies, and an additional 6 studies were identified by manual searching of reference lists (Figure 1). From these, we identified 144 potentially relevant studies for full-text review. A total of 20 studies were subsequently included, involving 529,741 subjects and 31,321 patients with AF on dialysis (Table 1 and Supplementary Tables 1 and 2). Of the these studies, 17 reported or provided data on associations of anticoagulation

Discussion

In this systematic review and meta-analysis of 20 observational studies involving 31,321 patients with AF and end-stage renal disease on dialysis, we found unexpected associations of anticoagulation use with outcomes. Anticoagulation use was expectedly associated with increased hemorrhagic stroke, increased bleeding, and lower risk of any thromboembolism. In contrast, there were unfavorable or nonsignificant associations of anticoagulation use with any stroke, ischemic stroke, cardiovascular

Disclosures

The authors have no conflicts of interest to disclose.

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    See page 1940 for disclosure information.

    Drs. Wong, Odutayo, and Emdin are supported by Rhodes Scholarships. Dr Wong is also supported by a Neil Hamilton Fairley Fellowship from the National Health and Medical Research Council of Australia. Dr Sun is supported by an Australian Postgraduate Award from the University of Adelaide.

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