Mortality associated with bevacizumab intravitreal injections in age-related macular degeneration patients after acute myocardial infarct: a retrospective population-based survival analysis

Graefes Arch Clin Exp Ophthalmol. 2018 Apr;256(4):651-663. doi: 10.1007/s00417-018-3917-9. Epub 2018 Feb 10.

Abstract

Background: Intraocular injections of antivascular endothelial growth factor (VEGF) agents are currently the main therapy in age-related macular degeneration (AMD). The safety of bevacizumab, an anti-VEGF compound frequently delivered off label, is debated, particularly for high-group risks. We aim to analyze the mortality associated with intravitreal injections of bevacizumab for AMD in patients previously diagnosed with acute myocardial infarct (MI).

Methods: In a national database, we identified bevacizumab-treated AMD patients with a diagnosis of MI prior to their first bevacizumab injection, delivered between September 2008 and October 2014 (n = 2100). We then generated sub-groups of patients treated within 3 months (n = 11), 6 months (n = 24), 12 months (n = 52), and 24 months (n = 124) after MI. Those patients were compared to age- and gender-matched members that had a MI at the same time and had never been exposed to anti-VEGF. Survival analysis was performed using propensity score-adjusted Cox regression.

Results: Bevacizumab-treated patients were slightly and insignificantly older than controls (mean age 83.25 vs 83.19 year, P = .75). Gender distribution was similar. In a Cox regression adjusted with propensity score, the following differences in mortality were found: within 3 months between MI and initiation of bevacizumab treatment, OR = 6.22 (95% C.I 1.08-35.97, P < .05); within 6 months, OR = 2.37 (95% C.I 0.93-6.02, P = .071); within 12 months, OR = 3.00 (95% C.I 1.44-6.28, P < .01); within 24 months after MI, OR = 2.24 (95% C.I 1.35-3.70, P < .01); and MI any time prior to first bevacizumab injection, OR = 1.71 (95% C.I 1.53-1.92, P < .001).

Conclusions: We report increased mortality associated with the use of intravitreal bevacizumab in AMD patients after MI, compared to age- and gender-matched post-MI patients with no exposure to any anti-VEGF agent. Caution should be taken while offering bevacizumab to AMD patients after MI.

Keywords: Anti-VEGF; Bevacizumab; Ischemic heart disease; Mortality; Myocardial infarct; Neovascular AMD; Safety.

Publication types

  • Multicenter Study

MeSH terms

  • Aged, 80 and over
  • Angiogenesis Inhibitors
  • Bevacizumab / administration & dosage
  • Bevacizumab / adverse effects*
  • Cause of Death / trends
  • Female
  • Follow-Up Studies
  • Humans
  • Intravitreal Injections / adverse effects
  • Israel / epidemiology
  • Male
  • Myocardial Infarction / complications
  • Myocardial Infarction / mortality*
  • Population Surveillance / methods*
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
  • Retrospective Studies
  • Survival Rate / trends
  • Time Factors
  • Visual Acuity
  • Wet Macular Degeneration / complications
  • Wet Macular Degeneration / diagnosis
  • Wet Macular Degeneration / drug therapy*

Substances

  • Angiogenesis Inhibitors
  • Bevacizumab
  • Receptors, Vascular Endothelial Growth Factor