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

  • Retinal Disorders
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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.

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Authors and Affiliations

  1. Department of Ophthalmology, Shaare Zedek Medical Center, 12 Beyt Street, 91031, Jerusalem, Israel

    Joel Hanhart

  2. Central Headquarters, Clalit Health Services, Tel Aviv, Israel

    Doron S. Comaneshter & Shlomo Vinker

  3. Mashav Applied Research, Jerusalem, Israel

    Yossi Freier-Dror

  4. Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel

    Shlomo Vinker

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  1. Joel Hanhart
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Doron S Comaneshter and Shlomo Vinker certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript. Joel Hanhart has given lectures for Novartis.

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Hanhart, J., Comaneshter, D.S., Freier-Dror, Y. et al. 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 256, 651–663 (2018). https://doi.org/10.1007/s00417-018-3917-9

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