Risk of intracranial hemorrhage with direct oral anticoagulants: an updated network meta-analysis of randomized controlled trials.

OBJECTIVE

We updated a network meta-analysis of randomized controlled trials to compare the risk of intracranial hemorrhage (ICH) between direct oral anticoagulants (DOACs) and Vitamin K Antagonists (VKAs) in detail across Venous thromboembolism and atrial fibrillation.

METHODS

PubMed, EMBASE, Web of Science, and the Cochrane Library databases were searched up to January 5, 2026. The incidence of ICH was investigated. Using frequentist network meta-analysis, interventions that were not compared directly could be compared indirectly by the 95% confidence interval (CI), making the search results more intuitive. Based on surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated.

RESULTS

Twenty randomised controlled trials (127,267 patients) were included. Compared with apixaban, VKAs (OR: 2.40, 95% CI: 1.62-3.56) had a higher risk of bleeding, and the difference was significant. Compared with dabigatran, rivaroxaban (OR: 1.89, 95% CI: 1.18-3.04) and VKAs (OR: 2.83, 95% CI: 2.00-3.99) had a higher risk of bleeding, and the difference was significant. Compared with edoxaban, rivaroxaban (OR: 1.60, 95% CI: 1.04-2.47) and VKAs (OR: 2.39; 95% CI: 1.81-3.17) had a higher risk of bleeding, and the difference was significant. Compared with rivaroxaban, VKAs (OR: 1.50; 95% CI: 1.08-2.07) had a higher risk of bleeding, and the difference was significant. In the ranking of the cumulative probability of ICH, dabigatran (SUCRA 87.6) had the highest safety, followed by apixaban (SUCRA 68.6), edoxaban (SUCRA 67.5), rivaroxaban (SUCRA 26.1), and VKAs (SUCRA 0.2).

CONCLUSIONS

All DOACs had a lower risk of ICH than VKAs. Dabigatran may be the safest choice among any anticoagulant regarding risk of ICH.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261336668, identifier CRD420261336668.