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

source extracted confidence: high 2026-04-09
#humans #atrial-fibrillation #dabigatran #anticoagulants #hemorrhage

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

Ma et al., 2023 | Eur J Clin Pharmacol | Systematic Review

Citation

Ma Fuxin, Xu Wenlin, ... Zhang Jinhua. 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

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.

Key Findings

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).

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population af
Sample Size 85826
Age Range See abstract
Condition See abstract

MeSH Terms

  • Humans
  • Atrial Fibrillation
  • Dabigatran
  • Anticoagulants
  • Hemorrhage
  • Stroke
  • Rivaroxaban
  • Fibrinolytic Agents
  • Vitamin K
  • Administration, Oral
  • Pyridines
  • Thiazoles

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Systematic Review, Journal Article, Network Meta-Analysis
  • Vertical: vitamin-k

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09