Risk analysis of new oral anticoagulants for gastrointestinal bleeding and intracranial hemorrhage in atrial fibrillation patients: a systematic review and network meta-analysis

J Zhejiang Univ Sci B. 2017 Jul;18(7):567-576. doi: 10.1631/jzus.B1600143.

Abstract

Background: Antithrombotic therapy using new oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) has been generally shown to have a favorable risk-benefit profile. Since there has been dispute about the risks of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH), we sought to conduct a systematic review and network meta-analysis using Bayesian inference to analyze the risks of GIB and ICH in AF patients taking NOACs.

Methods: We analyzed data from 20 randomized controlled trials of 91 671 AF patients receiving anticoagulants, antiplatelet drugs, or placebo. Bayesian network meta-analysis of two different evidence networks was performed using a binomial likelihood model, based on a network in which different agents (and doses) were treated as separate nodes. Odds ratios (ORs) and 95% confidence intervals (CIs) were modeled using Markov chain Monte Carlo methods.

Results: Indirect comparisons with the Bayesian model confirmed that aspirin+clopidogrel significantly increased the risk of GIB in AF patients compared to the placebo (OR 0.33, 95% CI 0.01-0.92). Warfarin was identified as greatly increasing the risk of ICH compared to edoxaban 30 mg (OR 3.42, 95% CI 1.22-7.24) and dabigatran 110 mg (OR 3.56, 95% CI 1.10-8.45). We further ranked the NOACs for the lowest risk of GIB (apixaban 5 mg) and ICH (apixaban 5 mg, dabigatran 110 mg, and edoxaban 30 mg).

Conclusions: Bayesian network meta-analysis of treatment of non-valvular AF patients with anticoagulants suggested that NOACs do not increase risks of GIB and/or ICH, compared to each other.

Keywords: Anticoagulation; New oral anticoagulant; Atrial fibrillation; Meta-analysis; Gastrointestinal bleeding; Intracranial hemorrhage.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Administration, Oral*
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Atrial Fibrillation / drug therapy*
  • Bayes Theorem
  • Clinical Trials as Topic
  • Dabigatran / administration & dosage
  • Dabigatran / adverse effects
  • Female
  • Gastrointestinal Hemorrhage / prevention & control*
  • Hemorrhage / prevention & control*
  • Humans
  • Intracranial Hemorrhages / prevention & control*
  • Male
  • Markov Chains
  • Middle Aged
  • Monte Carlo Method
  • Network Meta-Analysis
  • Odds Ratio
  • Pyridines / administration & dosage
  • Pyridines / adverse effects
  • Randomized Controlled Trials as Topic
  • Risk
  • Thiazoles / administration & dosage
  • Thiazoles / adverse effects
  • Warfarin / administration & dosage
  • Warfarin / adverse effects

Substances

  • Anticoagulants
  • Pyridines
  • Thiazoles
  • Warfarin
  • Dabigatran
  • edoxaban