Association of Novel Oral Antithrombotics With the Risk of Intraocular Bleeding

Abstract

IMPORTANCE 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. OBJECTIVE To determine the risk of developing intraocular hemorrhages with novel oral antithrombotic therapy compared with that of traditional antithrombotic agents. DESIGN, SETTING, AND PARTICIPANTS 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.MAIN OUTCOMES AND MEASURES 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. RESULTS 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). CONCLUSIONS AND RELEVANCEThese results suggest a decreased risk of intraocular hemorrhage associated with novel direct thrombin inhibitors and direct factor Xa inhibitors, but no difference for P2Y 12 inhibitors compared with traditional vitamin K anticoagulation and antiplatelet therapy, respectively.

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 .…”

“…NOACs are known to be non-inferior or even superior to warfarin for prevention of stroke and systemic embolism in patients with non-valvular AF, and also associated with lower rates of bleeding, especially life-threatening hemorrhage (e.g., intracranial bleeding) 3,13 . 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.…”

“…In terms of the safety in patients taking anticoagulants, intraocular bleeding is not a life-threatening 'major' complication, but is critical and can lead to severe visual loss and decrease vision-related quality of life. Previous studies have reported that there is an increased risk of intraocular bleeding with warfarin or other oral antithrombotics, raising concerns over the safety of these medications 9 . Hence, several studies on ocular diseases have examined the impact of anticoagulant therapy with NOAC, with a focus on ocular bleeding as a major safety issue [9][10][11] .…”

“…Previous studies have reported that there is an increased risk of intraocular bleeding with warfarin or other oral antithrombotics, raising concerns over the safety of these medications 9 . Hence, several studies on ocular diseases have examined the impact of anticoagulant therapy with NOAC, with a focus on ocular bleeding as a major safety issue [9][10][11] . While NOACs benefit patients with stroke and systemic thromboembolisms 12 , their efficacy on microvascular conditions, such as retinal vascular occlusion, requires further evaluation.…”

Antiplatelet and anticoagulant agents in vitreoretinal surgery: a prospective multicenter study involving 804 patients

“…In conclusion, millions of people are treated worldwide with antithrombotic agents, including new agents such as novel oral anticoagulants [7]. Every professional involved in health care should strive to offer the best strategy for a given patient taking antithrombotic therapy.…”