Safety of antithrombotic drugs in patients with atrial fibrillation and non-end-stage chronic kidney disease: Meta-analysis and systematic review

- No higher major bleeding risk is observed in comparison of warfarin with placebo/antiplatelet in AF and NECKD.
- DOACs reduce the major bleeding risk by 19% compared to warfarin in AF and NECKD.
- DOACs maintain superior to warfarin in lower major bleeding risk in AF and mild to moderate CKD.

ObjectiveTo evaluate the safety of antithrombotic drugs used in patients with both atrial fibrillation (AF) and non-end-stage chronic kidney disease (NECKD).MethodsA search was performed for studies on major bleeding outcomes in patients with concurrent AF and NECKD using Medline and Cochrane databases on 19th February, 2015. Fixed- or random-effects meta-analysis was adopted for evaluating pooled effect sizes according to whether heterogeneity existed.ResultsTwelve articles were included for analysis. Three studies evaluated AF patients who took warfarin vs. placebo/antiplatelet drugs in the presence of NECKD. No significant difference in major bleeding risk was observed according to the pooled analysis using the random-effects model (RR: 1.05, 95% CI: 0.74-1.36). The risk of a composite of major bleeding outcomes was reduced by 19% in patients randomized to direct oral anticoagulants (DOACs) compared to dose-adjusted warfarin from pooled data of three randomized controlled trials with regard to AF and NECKD (RR: 0.81, 95% CI: 0.75-0.88). This superiority of DOACs to warfarin maintained until the renal function was severely impaired.ConclusionsIn patients with AF and NECKD, no significant increase in the incidence of major bleeding outcomes was observed in warfarin use compared with placebo/antiplatelet drugs. DOACs reduced the risk of major bleeding by 19% compared to warfarin and further data-exploration indicated that the risk did not increase as renal function deteriorated during the renal status of mild to moderate impairment.