Abstract
Purpose
To assess the risk of intraocular hemorrhage with warfarin and new oral anticoagulants (NOACs).
Methods
We ascertained all reported cases of intraocular hemorrhage (vitreous, choroidal, or retinal) with warfarin and NOACs (including dabigatran, rivaroxaban, apixaban) from the World Health Organizations’s Vigibase database from 1968–2015. We used a disproportionality analysis to compute reported odds ratios (RORs) and corresponding 95% confidence by comparing the number of events with the study outcomes and study drugs compared with all other drugs reported to Vigibase. A harmful signal was deemed for a lower limit of the 95% confidence interval above 1.
Results
We identified 80 cases of intraocular hemorrhage (vitreous, choroidal, or retinal) with warfarin in the World Health Organizations’s Vigibase database from 1968–2015. A total of 156 cases of intraocular hemorrhage with NOACs (82 with rivaroxaban, 65 with dabigatran, 9 with apixaban). Warfarin had the highest signal of association with choroidal hemorrhage (ROR= 65.40 (33.86–126.30)). Rivaroxaban had the highest signal of association with both retinal and vitreous hemorrhage (ROR=7.41 (5.73–9.59) and ROR= 11.14 (7.37–16.86), respectively). Dabigatran was also significantly associated with retinal and vitreous hemorrhage (ROR= 3.78 (2.82–5.08) and ROR= 5.83 (3.66–9.30), respectively). The number of reports of retinal and vitreous hemorrhage were also significantly higher with apixaban, but the number of cases may be too little to make a meaningful evaluation.
Conclusion
A signal for risk of intraocular hemorrhage was detected for warfarin, dabigatran, and rivaroxaban. Large epidemiologic studies are needed to further confirm these findings.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Johnson & Johnson 2014 Johnson & Johnson Annual Report. Available at: http://files.shareholder.com/downloads/JNJ/194526085x0x815170/816798CD-60D9-4653-BB5A-50A66FD5B9E7/JNJ_2014_Annual_Report_bookmarked_.pdf (accessed on 25 February 2016).
Lauffenburger J, Farley J, Gehi A, Rhoney D, Brookhart M, Fang G . Factors driving anticoagulant selection in patients with atrial fibrillation in the united states. Am J Cardiol 2015; 115 (8): 1095–1101.
Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365 (10): 883–891.
Wadhera RK, Russell CE, Piazza G . Warfarin versus novel oral anticoagulants: how to choose? Circulation 2014; 130 (22): e191–e193.
Madan S, Shah S, Partovi S, Parikh SA . Use of novel oral anticoagulant agents in atrial fibrillation: current evidence and future perspective. Cardiovasc Diagn Ther 2014; 4 (4): 314–323.
Caldeira D, Canastro M, Barra M, Ferreira A, Costa J, Pinto FJ et al. Risk of substantial intraocular bleeding with novel oral anticoagulants: Systematic review and meta-analysis. JAMA Ophthalmol 2015; 133 (7): 834–839.
Weir CR, Nolan DJ, Holding D, Hammer H . Intraocular haemorrhage associated with anticoagulant therapy. Acta Ophthalmol Scand 2000; 78 (4): 492–493.
Bloome MA, Ruiz RS . Massive spontaneous subretinal hemorrhage. Am J Ophthalmol 1978; 86 (5): 630.
Brown GC, Tasman WS, Shields JA . Massive subretinal hemorrhage and anticoagulant therapy. Can J Ophtalmol 1982; 17 (5): 227–230.
Koehler M, Sholiton D . Spontaneous hyphema resulting from warfarin. Ann Ophthalmol 1983; 15 (9): 858–861.
Levine MN, Raskob G, Hirsh J . Risk of haemorrhage associated with long term anticoagulant therapy. Drugs 1985; 30 (5): 444.
Lewis H, Sloan SH, Foos RY . Massive intraocular hemorrhage associated with anticoagulation and age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 1988; 226 (1): 59–64.
Kang TS, Lord K, Kunjukunju N . Spontaneous choroidal hemorrhage in a patient on dabigatran etexilate (pradaxa). Retin Cases Brief Rep 2014; 8 (3): 175–177.
Nguyen TM, Phelan MP, Werdich XQ, Rychwalski PJ, Huff CM . Subconjunctival hemorrhage in a patient on dabigatran (Pradaxa). Am J Emerg Med 2013; 31 (2): 455e3–455e.
Wang K, Ehlers JP . Bilateral spontaneous hyphema, vitreous hemorrhage, and choroidal detachment with concurrent dabigatran etexilate therapy. Ophthalmic Surg Lasers Imaging Retina 2016; 47 (1): 78–80.
Jun J, Hwang J . Association of rivaroxaban anticoagulation and spontaneous vitreous hemorrhage. JAMA Ophthalmol 2015; 133 (10): 1184–1186.
Sakaeda T, Tamon A, Kadoyama K, Okuno Y . Data mining of the public version of the FDA adverse event reporting system. Int J Med Sci 2013; 10 (7): 796–803.
Zink R Disproportionality analysis and its application to spontaneously reported adverse events in pharmacovigilance. Statistical Discovery. Available at: http://www.jmp.com/content/dam/jmp/documents/en/white-papers/disproportionality-105686.pdf (accessed on 29 September 2015).
Eliquis (apixaban) FDA Approval History—Drugs.com. (n.d.). Available at: http://www.drugs.com/history/eliquis.html (Retrieved on 11 March 2016).
Mason J, Frederick P, Neimkin M, White M, Feist R, Thomley M et al. Incidence of hemorrhagic complications after intravitreal bevacizumab (avastin) or ranibizumab (lucentis) injections on systemically anticoagulated patients. Retina 2010; 30 (9): 1386–1389.
Giansanti F, Eandi C, Virgili G . Submacular surgery for choroidal neovascularisation secondary to age-related macular degeneration. Cochrane Database Syst Rev 2009; 15 (2): CD006931.
Almenoff J, Tonning JM, Gould AL, Szarfman A, Hauben M, Ouellet-Hellstrom R et al2005 Perspectives on the use of data mining in pharmacovigilance. Drug Saf 28 (11): 981–1007.
Acknowledgements
World Health Organization (WHO) data was received from the WHO Collaborating Centre for International Drug Monitoring in Uppsala, Sweden. The information provided does not represent the opinions of either organization.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Talany, G., Guo, M. & Etminan, M. Risk of intraocular hemorrhage with new oral anticoagulants. Eye 31, 628–631 (2017). https://doi.org/10.1038/eye.2016.265
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/eye.2016.265
This article is cited by
-
Efficacy and safety of non-vitamin K-antagonist oral anticoagulants for retinal vascular diseases in patients with atrial fibrillation: Korean cohort study
Scientific Reports (2020)
-
Safety of cataract surgery in patients treated with the new oral anticoagulants (NOACs)
Graefe's Archive for Clinical and Experimental Ophthalmology (2019)
-
Antiplatelet and anticoagulant agents in vitreoretinal surgery: a prospective multicenter study involving 804 patients
Graefe's Archive for Clinical and Experimental Ophthalmology (2018)
