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

Thromb Res. 2016 Jan:137:46-52. doi: 10.1016/j.thromres.2015.11.020. Epub 2015 Nov 21.

Abstract

Objective: To evaluate the safety of antithrombotic drugs used in patients with both atrial fibrillation (AF) and non-end-stage chronic kidney disease (NECKD).

Methods: A 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.

Results: Twelve 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.

Conclusions: In 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.

Keywords: Atrial fibrillation; Direct oral anticoagulants; Major bleeding; Non-end-stage chronic kidney disease; Warfarin.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / epidemiology*
  • Comorbidity
  • Female
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use*
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology*
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic / drug therapy
  • Renal Insufficiency, Chronic / epidemiology*
  • Risk Factors
  • Thrombosis / epidemiology
  • Thrombosis / prevention & control*
  • Warfarin / adverse effects
  • Warfarin / therapeutic use

Substances

  • Fibrinolytic Agents
  • Warfarin