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Intraocular bleeding in patients managed with novel oral anticoagulation and traditional anticoagulation: a network meta-analysis and systematic review
  1. Kevin Phan1,
  2. Declan Lloyd2,
  3. Ash Wilson-Smith3,
  4. Vannessa Leung4,
  5. Marko Andric1
  1. 1 Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia
  2. 2 School of Medicine, The University of Notre Dame Sydney, Sydney, New South Wales, Australia
  3. 3 Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia
  4. 4 Sydney Eye Hospital, Sydney, New South Wales, Australia
  1. Correspondence to Declan Lloyd, School of Medicine, The University of Notre Dame, Sydney, NSW 2010, Australia; declan.lloyd1{at}


Background/aim To clarify the nature of the relationship between novel oral anticoagulants (NOACs) and traditional anticoagulation in respect to intraocular bleeding.

Methods A comprehensive literature search up to October 2017 yielded 12 randomised controlled trials. Bayesian Markov chain Monte Carlo analysis was employed to investigate the relationship across multiple trials with varying NOACs. Random effects (informative priors) ORs were applied for the risk of intraocular bleeding due to various treatment measures. Mantel-Haenszel pairwise analyses were also performed. A total of 102 617 participants from 12 different randomised controlled trials. 11 746 received apixaban, 16 074 received dabigatran, 18 132 received edoxaban, 11 893 received rivaroxaban and 44 764 received warfarin.

Results Edoxaban was significantly associated with a reduced risk of intraocular bleeding in comparison to warfarin (OR 0.59; 95% CI 0.34 to 0.98). All other findings were non-significant; however, apixaban was the only NOAC to trend with an increased event rate against warfarin. The Bayesian Markov chain Monte Carlo modelling indicated that edoxaban had the greatest chance of producing the lowest rate of bleeding (surface under the cumulative ranking curve 0.8642). Pooled pairwise analysis supported the network analysis results favouring edoxaban against warfarin (OR 0.59; 95% CI 0.39 to 0.90; p=0.02) as well as subgroup analysis of low-dose edoxaban versus warfarin (OR 0.43; 95% CI 0.24 to 0.78).

Conclusion The analysis suggests that edoxaban may be the paramount agent in reducing intraocular bleeding rates. Given a paucity of reporting data for this rare event, future research and confirmation is strongly recommended.

  • pharmacology
  • drugs
  • intraocular bleeding

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  • Contributors KP: lead author, contributed to the study design, conception, writing and editing. DL: contributed to data acquisition and analysis, formatting, editing and writing. AW-S: contributed to data acquisition and analysis, editing and writing. VL: contributed to study design and gross editing. MA: contributed to the study design, editing and writing. All authors fulfil the criteria of the ICMJE Recommendations (2013).

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All data associated with our study are published within the manuscript.

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