title: Adverse events with intravitreal injection of vascular endothelial growth factor inhibitors: nested case-control study.
abstract: OBJECTIVE
  To assess the risk of systemic adverse events associated with intravitreal injections of vascular endothelial growth factor inhibiting drugs.
  
  
  METHODS
  Population based nested case-control study.
  
  
  METHODS
  Ontario, Canada.
  
  
  METHODS
  91,378 older adults with a history of physician diagnosed retinal disease identified between 1 April 2006 and 31 March 2011. Cases were 1477 patients admitted to hospital for ischaemic stroke, 2229 admitted for an acute myocardial infarction, 1059 admitted or assessed in an emergency department for venous thromboembolism, and 2623 admitted for congestive heart failure. Event-free controls (at a ratio of 5:1) were matched to cases on the basis of year of birth, sex, history of the outcome in the previous 5 years, and diabetes.
  
  
  METHODS
  Exposure to vascular endothelial growth factor inhibiting drugs identified within 180 days before the index date.
  
  
  RESULTS
  After adjustment for potential confounders, participants who had ischaemic stroke, acute myocardial infarction, congestive heart failure, or venous thromboembolism were not more likely than control participants to have been exposed to either bevacizumab (adjusted odds ratios of 0.95 (95% confidence interval 0.68 to 1.34) for ischaemic stroke, 1.04 (0.77 to 1.39) for acute myocardial infarction, 0.81 (0.49 to 1.34) for venous thromboembolism, and 1.21 (0.91 to 1.62) for congestive heart failure) or ranibizumab (adjusted odds ratios 0.87 (0.68 to 1.10) for ischaemic stroke, 0.90 (0.72 to 1.11) for acute myocardial infarction, 0.88 (0.67 to 1.16) for venous thromboembolism, and 0.87 (0.70 to 1.07) for congestive heart failure). Similarly, a secondary analysis of exclusive users of bevacizumab or ranibizumab showed no differences in risk between the two drugs (adjusted odds ratios for bevacizumab relative to ranibizumab of 1.03 (0.67 to 1.60) for ischaemic stroke, 1.23 (0.85 to 1.77) for acute myocardial infarction, 0.92 (0.51 to 1.69) for venous thromboembolism, and 1.35 (0.93 to 1.95) for congestive heart failure). These findings were consistent for all but one outcome in subgroup analyses.
  
  
  CONCLUSIONS
  Intravitreal injections of bevacizumab and ranibizumab were not associated with significant risks of ischaemic stroke, acute myocardial infarction, congestive heart failure, or venous thromboembolism.
authors: Department of Ophthalmology, Queen's University, Kingston, ON, Canada.
authors: Robert J
authors: RJ
authors: Campbell
authors: Sudeep S
authors: SS
authors: Gill
authors: Susan E
authors: SE
authors: Bronskill
authors: J Michael
authors: JM
authors: Paterson
authors: Marlo
authors: M
authors: Whitehead
authors: Chaim M
authors: CM
authors: Bell
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects*; D000068258:Bevacizumab; D002545:Brain Ischemia / Q000139:chemically induced* / Q000453:epidemiology; D016022:Case-Control Studies; D005260:Female; D006333:Heart Failure / Q000139:chemically induced*; D006801:Humans; D058449:Intravitreal Injections / Q000009:adverse effects*; D016015:Logistic Models; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000453:epidemiology; D009864:Ontario / Q000453:epidemiology; D000069579:Ranibizumab; D012164:Retinal Diseases / Q000188:drug therapy*; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced* / Q000453:epidemiology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D054556:Venous Thromboembolism / Q000139:chemically induced* / Q000453:epidemiology
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069579:Ranibizumab