Stroke rates after introduction of vascular endothelial growth factor inhibitors for macular degeneration: a time series analysis

Objective — To assess whether stroke rates among patients with retinal disease were influenced by the rapid and sequential uptakes of bevacizumab and ranibizumab for age-related macular degeneration (AMD).

Design — Population-based, time series analysis using encrypted, linked healthcare databases in Ontario, Canada.

Participants — The researchers included all patients aged 66 years or older with physician-diagnosed retinal disease in the previous 5 years between 2002 and 2010 (N = 116 388). A secondary analysis evaluated patients who had undergone photodynamic therapy (PDT) within the preceding year (N = 10 059).

Methods — The researchers used segmented regression analysis to evaluate changes in the rate of hospitalization for ischemic stroke associated with the introduction of bevacizumab and ranibizumab. The stroke rate was compared across 3 mutually exclusive periods: the period before the availability of bevacizumab or ranibizumab, the period of bevacizumab dominant AMD therapy, and the period of ranibizumab dominant AMD therapy.

Main Outcome Measures — Hospitalizations for ischemic stroke.

Results — Among patients with retinal disease, neither the trend nor the level of the stroke time series changed with the uptake of bevacizumab (trend change coefficient -0.0026 stroke hospitalizations/1000 subjects/month [95% confidence interval {CI}, -0.0066 to 0.0014; P = 0.20]; level change coefficient, 0.036 stroke hospitalizations/1000 subjects [95% CI, -0.070 to 0.14; P = 0.51]), or ranibizumab (trend change coefficient: -0.0011 stroke hospitalizations/1000 subjects/month [95% CI, -0.0087 to 0.0065; P = 0.78]; level change coefficient: -0.017 stroke hospitalizations/1000 subjects [95% CI, -0.14 to 0.11; P = 0.79]). Similar results were observed in the analysis restricted to patients with recent PDT and in analyses stratified on age, sex, history of stroke, and history of diabetes.

Conclusions — The rapid uptake of vascular endothelial growth factor (VEGF) inhibitors for AMD was not associated with a change in the rate of hospitalization for stroke among Ontario seniors with retinal disease. Furthermore, stroke rates in the bevacizumab and ranibizumab periods were not different. These population-level results complement the findings of a recently published trial comparing bevacizumab and ranibizumab, and may assist clinicians and policy makers as they balance the comparative efficacy, safety, and cost of these 2 closely related treatments.