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Ophthalmology. 2012 Aug;119(8):1604-8. doi: 10.1016/j.ophtha.2012.05.028. Epub 2012 Jun 19.

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

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1
Department of Ophthalmology, Queen's University, Kingston, Canada. rob.campbell@queensu.ca

Abstract

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:

We 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:

We 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.

PMID:
22717458
DOI:
10.1016/j.ophtha.2012.05.028
[Indexed for MEDLINE]
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