Document Detail

Stroke rates after introduction of vascular endothelial growth factor inhibitors for macular degeneration: a time series analysis.
MedLine Citation:
PMID:  22717458     Owner:  NLM     Status:  MEDLINE    
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.
Robert J Campbell; Chaim M Bell; J Michael Paterson; Susan E Bronskill; Rahim Moineddin; Marlo Whitehead; Sudeep S Gill
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-06-19
Journal Detail:
Title:  Ophthalmology     Volume:  119     ISSN:  1549-4713     ISO Abbreviation:  Ophthalmology     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-03     Completed Date:  2012-10-25     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  7802443     Medline TA:  Ophthalmology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1604-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Department of Ophthalmology, Queen's University, Kingston, Canada.
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MeSH Terms
Aged, 80 and over
Angiogenesis Inhibitors / administration & dosage*,  therapeutic use
Antibodies, Monoclonal, Humanized / administration & dosage*,  therapeutic use
Databases, Factual
Hospitalization / statistics & numerical data
Intravitreal Injections
Macular Degeneration / drug therapy*
Risk Assessment
Stroke / epidemiology*
Time Factors
Treatment Outcome
Vascular Endothelial Growth Factor A / antagonists & inhibitors*
Grant Support
MOP 106693//Canadian Institutes of Health Research
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Antibodies, Monoclonal, Humanized; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A; 0/ranibizumab; 2S9ZZM9Q9V/bevacizumab

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