Non-major bleeding risk of direct oral anticoagulants versus vitamin K antagonists for stroke prevention with atrial fibrillation: a systematic review and network meta-analysis

Eur J Clin Pharmacol. 2023 Aug;79(8):1013-1022. doi: 10.1007/s00228-023-03520-5. Epub 2023 Jun 13.

Abstract

Background: Direct oral anticoagulants (DOACs) are associated with bleeding. Patients often stop taking DOACs due to non-major bleeding, which may lead to stroke recurrence. We aimed to determine the risk of non-major bleeding using different DOACs to prevent strokes in atrial fibrillation (AF).

Methods: A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting non-major bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated.

Results: Nineteen randomized controlled trials (RCTs) (involving 85,826 patients) were included. For clinically relevant non-major bleeding, the risk for bleeding was lowest for apixaban (SUCRA, 93.9), followed by that for VKAs (SUCRA, 47.7), dabigatran (SUCRA, 40.3), rivaroxaban (SUCRA, 35.9), and edoxaban (SUCRA, 32.2). The minor bleeding safety of DOACs was ranked from highest to lowest as follows: apixaban (SUCRA, 78.1), edoxaban (SUCRA, 69.4), dabigatran (SUCRA, 48.8), and VKAs (SUCRA, 3.7).

Conclusions: Based on current evidence, for stroke prevention in patients with AF, the safest DOAC is apixaban in terms of non-major bleeding. This suggests that apixaban may have a lower risk of non-major bleeding than other anticoagulants and may help provide some clinical reference for choosing a more appropriate drug for the patient.

Keywords: Atrial fibrillation; Clinically relevant non-major bleeding; Direct oral anticoagulant; Stroke; Vitamin K antagonist.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review

MeSH terms

  • Administration, Oral
  • Anticoagulants / adverse effects
  • Atrial Fibrillation* / complications
  • Atrial Fibrillation* / drug therapy
  • Dabigatran / adverse effects
  • Fibrinolytic Agents / therapeutic use
  • Hemorrhage / chemically induced
  • Humans
  • Network Meta-Analysis
  • Rivaroxaban / therapeutic use
  • Stroke* / etiology
  • Stroke* / prevention & control
  • Vitamin K

Substances

  • edoxaban
  • Dabigatran
  • Anticoagulants
  • Rivaroxaban
  • Fibrinolytic Agents
  • Vitamin K