Association of Novel Oral Antithrombotics With the Risk of Intraocular Bleeding

Antithrombotics, Risk, Intraocular Bleeding

2017 Dec 14. doi: 10.1001/jamaophthalmol.2017.5677. [Epub ahead of print]

Association of Novel Oral Antithrombotics With the Risk of Intraocular Bleeding.



Novel oral anticoagulation and antiplatelet therapies have become a mainstay of treatment for thromboembolic disease. However, the safety profile of these medications has not been completely characterized.


To determine the risk of developing intraocular hemorrhages with novel oral antithrombotic therapy compared with that of traditional antithrombotic agents.


In this retrospective cohort study, a large national insurance claims database was used to generate 2 parallel analyses. All patients with incident use of dabigatran etexilate or rivaroxaban between January 1, 2010, and September 30, 2015, were compared with patients with incident use of warfarin sodium. Similarly, patients with new use of prasugrel hydrochloride were compared with those with new use of clopidogrel bisulfate. Both analyses required the patient to be in the insurance plan for at least 24 months prior to initiation of therapy and excluded patients with any previous diagnosis of intraocular hemorrhages or any prescription for the comparator medications. Furthermore, the antiplatelet analysis required a diagnosis of acute coronary syndrome or a myocardial infarction within 60 days of initiation of pharmacologic therapy. The anticoagulant analysis excluded patients with end-stage renal disease, renal transplants, and those with heart valve disease.


Incident intraocular hemorrhages at 90 and 365 days. Multivariate Cox proportional hazards regression models were used to compare the hazard ratio (HR) of developing an intraocular hemorrhage in individuals taking novel agents compared with those taking traditional medications.


A total of 146 137 patients taking warfarin (76 714 women and 69 423 men; mean [SD] age, 69.8 [11.8] years) were compared with 64 291 patients taking dabigatran or rivaroxaban (31 576 women and 32 715 men; mean [SD] age, 67.6 [11.7] years). Cox proportional hazards regression revealed a decreased hazard for developing an intraocular hemorrhage with dabigatran or rivaroxaban at 365 days (HR, 0.75; 95% CI, 0.58-0.97; P = .03), but not at 90 days (HR, 0.73; 95% CI, 0.22-2.63; P = .13). A total of 103 796 patients taking clopidogrel (37 578 women and 66 218 men; mean [SD] age, 68.0 [11.3] years) were compared with 8386 patients taking prasugrel (1988 women and 6380 men; mean [SD] age, 61.0 [9.6] years) and no increased hazard for developing an intraocular hemorrhage with prasugrel was seen at 90 days (HR, 0.75; 95% CI, 0.29-1.92; P = .55) or 365 days (HR, 1.19; 95% CI, 0.69-2.04; P = .53).

Antithrombotics, Risk, Intraocular Bleeding  CONCLUSIONS AND RELEVANCE:

These results suggest a decreased risk of intraocular hemorrhage associated with novel direct thrombin inhibitors and direct factor Xa inhibitors, but no difference for P2Y12 inhibitors compared with traditional vitamin K anticoagulation and antiplatelet therapy, respectively.


Stroke risk among adult patients with third, fourth or sixth cranial nerve palsy: a Nationwide Cohort Study

Stroke, risk, adult, third, fourth or sixth cranial nerve palsy, Cohort Study

2017 Aug 3. doi: 10.1111/aos.13488. [Epub ahead of print]

Stroke risk among adult patients with third, fourth or sixth cranial nerve palsy: a Nationwide Cohort Study.



This study sought to determine whether isolated third, fourth and sixth cranial nerve palsies (NPs) are associated with increased short- and long-term risk of a subsequent stroke.


This was a nationwide retrospective propensity score-matched cohort study. A cohort of patients with NP (n = 466) and a randomly selected, propensity-matched control cohort (n = 2281) were extracted from the Korean national insurance claim database. Subjects were tracked for 5 years total, subdivided into periods of 0-1 years, 1-3 years and 3-5 years. We assessed the risk of stroke using hazard ratios (HRs) and confidence intervals (CIs) after adjustments using Cox regression at different time intervals.


The median follow-up was 3.1 years. Stroke developed in 18.9% of the NP cohort and 7.5% of the control cohort. Stroke risk after NP was highest in the first year [14.7 per 100 person-year at 0-1 years (HR = 6.6), 3.1 per 100 person-year at 1-3 years (HR = 1.6) and 4.3 per 100 person-year at 3-5 years (HR = 2.8)]. Each type of NP was also associated with stroke risk: within 0-1 years, stroke risk was increased in third (HR = 7.6), fourth (HR = 6.0) and sixth (HR = 5. 84) NPs. In the 3- to 5-year period, risk was increased in sixth (HR = 4.7) and fourth (HR = 3.3) NPs, but not third (HR = 0.6) NPs.


Patients in the NP cohort were more likely to have a stroke than those in the matched control cohort; the increased risk was both time- and cranial nerve-dependent.

Stroke, risk, adult, third, fourth or sixth cranial nerve palsy, Cohort Study


cranial nerve palsy; fourth nerve palsy; sixth nerve palsy; stroke; third nerve palsy

Risk of Intraocular Bleeding With Novel Oral Anticoagulants Compared With Warfarin

Risk, Intraocular Bleeding, Anticoagulant, Warfarin

2017 Jul 6. doi: 10.1001/jamaophthalmol.2017.2199. [Epub ahead of print]

Risk of Intraocular Bleeding With Novel Oral Anticoagulants Compared With Warfarin: A Systematic Review and Meta-analysis.



It is unclear if the risk of intraocular bleeding with novel oral anticoagulants differs compared with warfarin.


To characterize the risk of intraocular bleeding with novel oral anticoagulants compared with warfarin.


A systematic review and meta-analysis was undertaken in an academic medical setting. MEDLINE and were searched for randomized clinical trials published up until August 2016. This search was supplemented by manual bibliography searches of identified trials and other review articles.


Studies were eligible for inclusion if they were phase 3 randomized clinical trials, enrolled patients with atrial fibrillation or venous thromboembolism, compared a novel oral anticoagulant (dabigatran, rivaroxaban, apixaban, or edoxaban) with warfarin, and recorded event data on intraocular bleeding. Data on intraocular bleeding were pooled using inverse-variance, weighted, fixed-effects meta-analysis.


The PRISMA guidelines were used for abstracting data and assessing quality. Independent extraction was performed by 2 investigators.


Intraocular bleeding events and associated risk ratio for novel oral anticoagulants compared with warfarin.


Twelve trials investigating 102 627 patients were included. Randomization to novel oral anticoagulants was associated with a 22% relative reduction in intraocular bleeding compared with warfarin (risk ratio, 0.78; 95% CI, 0.61-0.99). There was no significant heterogeneity observed (I2 = 4.8%, P = .40). Comparably lower risks of intraocular bleeding with novel oral anticoagulants were seen in subgroup analyses, with no significant difference according to the indication for anticoagulation (P for heterogeneity = .49) or the novel oral anticoagulant type (P for heterogeneity = .15). Summary estimates did not differ materially when random-effects meta-analytic techniques were used.


These results suggest that novel oral anticoagulants reduce the risk of intraocular bleeding by approximately one-fifth compared with warfarin. Similar benefits were seen in both patients with atrial fibrillation and venous thromboembolism. Our data have particular relevance for patients at higher risk of spontaneous retinal and subretinal bleeding. These findings may also have important implications in the perioperative period, in which the use of novel oral anticoagulants may be superior. Future studies are required to better characterize the optimal management of patients with both ophthalmic disease and cardiovascular comorbidities requiring anticoagulation.