Risk of Intraocular Bleeding With Novel Oral Anticoagulants Compared With Warfarin

Abstract

IMPORTANCE It is unclear if the risk of intraocular bleeding with novel oral anticoagulants differs compared with warfarin.OBJECTIVE To characterize the risk of intraocular bleeding with novel oral anticoagulants compared with warfarin.DATA SOURCES A systematic review and meta-analysis was undertaken in an academic medical setting. MEDLINE and ClinicalTrials.gov 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.STUDY SELECTION 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. DATA EXTRACTION AND SYNTHESISThe PRISMA guidelines were used for abstracting data and assessing quality. Independent extraction was performed by 2 investigators. MAIN OUTCOMES AND MEASURESIntraocular bleeding events and associated risk ratio for novel oral anticoagulants compared with warfarin.RESULTS 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 (I 2 = 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. CONCLUSIONS AND RELEVANCEThese 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.

Efficacy and safety of non-vitamin K-antagonist oral anticoagulants for retinal vascular diseases in patients with atrial fibrillation: Korean cohort study

“…intraocular bleeding, all the NOACs showed a lower risk of bleeding than did warfarin. This is similar to previous cohort studies which reported a reduced risk for intraocular bleeding 9,15 . Few guidelines have addressed the issue of anticoagulant use for treatment of retinal vascular occlusions and the possible risk for intraocular bleeding 21,26 .…”

“…A cohort study reported that the incidence of intraocular bleeding was less in NOAC (dabigatran and rivaroxaban) users compared to that of warfarin users 9 . Other meta-analyses also revealed a lower risk of intraocular bleeding with NOAC use 14,15 , suggesting the safety of NOAC for intraocular bleeding.…”

“…Second, we could not investigate the difference between standard-dose NOAC users and low-dose NOAC users. As mentioned above, Asia shows a tendency for prescribing lower doses than do Western countries 15,29 . We could not classify the patients according to dose as many patients changed the dose during the study period.…”

Efficacy and safety of novel oral anticoagulants versus vitamin K antagonists in the treatment of venous thromboembolism

“…Patients with atrial fibrillation and venous thromboembolism have similar benefits. The results of the study are instructive for the selection of anticoagulant drugs in patients with high risk of retinal and subretinal hemorrhage, and preference should be given to NOACs during perioperative period (Sun et al, 2017). Furthermore, some investigators investigated the correlation between anticoagulants (warfarin vs NOACs) and death from intracerebral hemorrhage.…”

Intraocular bleeding in patients managed with novel oral anticoagulation and traditional anticoagulation: a network meta-analysis and systematic review

“…However, the evidence of the association between NOAC treatment and intraocular bleeding remains inconsistent; to date, no analyses have been conducted to simultaneously and head-to-head compare the rates of intraocular bleeding in patients on the different NOAC agents versus and traditional anticoagulation. Two predominant meta-analyses on this topic, by Caldeira et al 1 and Sun et al ,2 unfortunately present contradictory findings; Caldeira et al found no difference in the risk of substantial intraocular bleeding between NOACs and traditional anticoagulation, whereas Sun et al claimed risk reductions of up to 20% in NOAC cohorts. The analyses are primarily hindered by the pooling of NOACs, which obscures the individual NOAC subgroup outcomes, in addition to heavily using data from inadequately powered trials.…”