Ocular Neovascular Conversion and Systemic Bleeding Complications in Patients with Age-Related Macular Degeneration on Anticoagulants

Purpose

Conversion to neovascular disease in patients with non-neovascular age-related macular degeneration (AMD) initiated on direct oral anticoagulants (DOACs) compared with matched patients treated with warfarin.

Design

Retrospective cohort study.

Participants

The study included 20 300 patients and 13 387 patients with non-neovascular AMD initiated on DOACs or warfarin, respectively, before propensity score matching (PSM).

Methods

TriNetX was used to identify patients diagnosed with non-neovascular AMD stratified by treatment with DOACs or warfarin with at least 6 months of follow-up. Propensity score matching was performed to control for baseline demographics and medical comorbidities.

Main Outcome Measures

Relative risk (RR) of developing neovascular AMD, macular hemorrhage (MH), vitreous hemorrhage (VH), and requiring an ocular intervention (intravitreal anti-VEGF therapy or pars plana vitrectomy [PPV]) within 6 months and 1 year. Patients with chronic atrial fibrillation (AF) on anticoagulation were separately evaluated for the same measures within 5 years after initiating therapy.

Results

Treatment with warfarin was associated with a higher risk of developing neovascular AMD at 6 months (RR, 1.24, 95% confidence interval [CI], 1.12–1.39; P < 0.001) and 1 year (RR, 1.26, 95% CI, 1.14–1.40; P < 0.001) when compared with matched patients treated with DOACs. There was an increased risk of requiring intravitreal anti-VEGF therapy (6 months: RR, 1.30; 95% CI, 1.13–1.49; P < 0.001; 1 year: RR, 1.31, 95% CI, 0.72–2.05; P < 0.001) and PPV (6 months: RR, 2.13; 95% CI, 1.16–3.94; P = 0.01; 1 year: RR, 2.29, 95% CI, 1.30–4.05; P = 0.003). Among patients with AMD and AF treated with warfarin, there was an increased risk of ocular complications (neovascular AMD: RR, 1.25; 95% CI, 1.14–1.38; P < 0.001; MH: RR, 1.86; 95% CI, 1.47–2.35; P < 0.001; VH: RR, 2.22; 95% CI, 1.51–3.26; P < 0.001) and need for intravitreal anti-VEGF therapy (RR, 1.34; 95% CI, 1.18–1.52; P < 0.001) over an extended 5-year period. There was no significant difference in the development of major systemic hemorrhagic events between the 2 cohorts over 5 years.

Conclusions

Patients with non-neovascular AMD treated with warfarin were more likely to develop neovascular disease and require ocular intervention for hemorrhagic complications when compared with matched patients initiated on DOACs.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.