title: Risk of Myocardial Infarction and Stroke With Single or Repeated Doses of Intravitreal Bevacizumab in Age-Related Macular Degeneration.
abstract: OBJECTIVE
  To examine the risk of myocardial infarction and stroke with single and repeated doses of intravitreal bevacizumab in wet age-related macular degeneration (AMD).
  
  
  METHODS
  Nested case-control study and retrospective cohort study.
  
  
  METHODS
  setting: Two patient cohorts from British Columbia, Canada.
  
  
  METHODS
  Patients with wet AMD.
  
  
  METHODS
  For the cohort study, patients who received the first intravitreal bevacizumab; for the nested case-control study, repeated injections of intravitreal bevacizumab.
  
  
  METHODS
  Myocardial infarction for the retrospective cohort study; myocardial infarction and stroke for the nested case-control study.
  
  
  RESULTS
  In the cohort analysis, there were 2564 AMD subjects not on a vascular endothelial growth factor (VEGF) inhibitor and 5644 subjects receiving intravitreal bevacizumab. The rate of myocardial infarction (MI) among bevacizumab users was 11/1000 person-years, compared to 14.9/1000 person-years in nonusers. The adjusted rate ratio (RR) for MI was 0.70 (95% confidence interval [CI]: 0.50-1.00) and 0.74 (0.46-1.20) for the propensity score-adjusted analysis. In the nested case-control analysis there were 7452 new users of VEGF inhibitors, within which there were 313 cases of MI with 3130 matched controls. The adjusted RR for MI among those receiving 3 or more injections compared to those receiving fewer than 3 was 0.71 (95% CI: 0.41-1.22). Also in the nested case-control analysis, the adjusted RR for stroke was 0.81 (95% CI: 0.39-1.65) for those receiving ≥4 injections vs those receiving fewer than 4 injections.
  
  
  CONCLUSIONS
  Single or repeated doses of intravitreal bevacizumab were not shown to increase the risk of myocardial infarction or stroke in patients with wet AMD.
authors.affiliation: Pharmaceutical Outcomes Programme, British Columbia Children Hospital, Vancouver, Canada; Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada. Electronic address: etminanm@mail.ubc.ca.
authors.forename: Mahyar
authors.initials: M
authors.lastname: Etminan
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Maberley
authors.affiliation: Cardiac Services BC, Provincial Health Services Authority, Vancouver, Canada.
authors.forename: David W
authors.initials: DW
authors.lastname: Babiuk
authors.affiliation: Pharmaceutical Outcomes Programme, British Columbia Children Hospital, Vancouver, Canada; Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Carleton
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000009:adverse effects; D001955:British Columbia / Q000453:epidemiology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced / Q000453:epidemiology*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced / Q000453:epidemiology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D057135:Wet Macular Degeneration / Q000188:drug therapy*
chemical_list: D020533:Angiogenesis Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab