VEGF Inhibition in Retinal Vein Occlusion Does Not Associate with Cardiovascular Morbidity or Mortality

Intravitreal treatment with VEGF inhibitors has proven safe in clinical trials, but often on selected patient groups and without statistical power to investigate rare safety events. Data on anti-VEGF treatment in patients with retinal vein occlusion (RVO) are sparsely represented, and studies provid...

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Veröffentlicht in:Ophthalmology retina 2023-08, Vol.7 (8), p.652-660
Hauptverfasser: Frederiksen, Katrine Hartmund, Stokholm, Lonny, Möller, Sören, Thinggaard, Benjamin Sommer, Kawasaki, Ryo, Peto, Tunde, Grauslund, Jakob
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container_end_page 660
container_issue 8
container_start_page 652
container_title Ophthalmology retina
container_volume 7
creator Frederiksen, Katrine Hartmund
Stokholm, Lonny
Möller, Sören
Thinggaard, Benjamin Sommer
Kawasaki, Ryo
Peto, Tunde
Grauslund, Jakob
description Intravitreal treatment with VEGF inhibitors has proven safe in clinical trials, but often on selected patient groups and without statistical power to investigate rare safety events. Data on anti-VEGF treatment in patients with retinal vein occlusion (RVO) are sparsely represented, and studies providing population-based, long-term follow-up are needed to assess the risks in routine clinical practice. We aimed to evaluate the association between treatment with anti-VEGF and the risk of incident cardiovascular disease (CVD) and all-cause mortality in patients with RVO, and whether this association was affected by selected risk factors. A cohort study from January 2012 to December 2018 using Danish nationwide registries linked on an individual level. Patients with RVO (n = 7235), exposed (n = 3508), and unexposed (n = 3727) to anti-VEGF, aged ≥ 40 years, alive, and living in Denmark. Cox proportional hazards analysis evaluating the effect of intravitreal VEGF inhibitory treatment on incident CVD and all-cause mortality. A predefined analysis plan specified primary outcomes as hazard ratios (HRs) of a composite CVD endpoint and all-cause mortality in patients treated with anti-VEGF compared with untreated. Secondary outcomes included cumulative dose analysis, HRs on subgroups of CVD, and stratified analyses evaluating the effect of sex, age, diabetes, intensive treatment, and preexisting CVD on the HRs. We found no increased risk of composite CVD (HR, 1.07; 95% confidence interval [CI], 0.89–1.29) or all-cause mortality (HR, 0.88; 95% CI, 0.77–1.00) in patients with RVO treated with anti-VEGF. In the secondary analyses, we found no dose-response relationship. We found an increased risk of intracranial hemorrhage (HR, 1.66; 95% CI, 1.02–2.71), but no increased risks in remaining subgroups of CVD. We found no increased risk associated with selected predisposing risk factors, and no increased risk in patients with preexisting CVD. Treatment with anti-VEGF in patients with RVO is safe, when evaluated in a nationwide, population-based setting. An increased risk of intracranial hemorrhage might be present, but cannot be reliably quantified and should be further elucidated by larger population-based studies including all indications for anti-VEGF treatment. Proprietary or commercial disclosure may be found after the references.
doi_str_mv 10.1016/j.oret.2023.02.009
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Data on anti-VEGF treatment in patients with retinal vein occlusion (RVO) are sparsely represented, and studies providing population-based, long-term follow-up are needed to assess the risks in routine clinical practice. We aimed to evaluate the association between treatment with anti-VEGF and the risk of incident cardiovascular disease (CVD) and all-cause mortality in patients with RVO, and whether this association was affected by selected risk factors. A cohort study from January 2012 to December 2018 using Danish nationwide registries linked on an individual level. Patients with RVO (n = 7235), exposed (n = 3508), and unexposed (n = 3727) to anti-VEGF, aged ≥ 40 years, alive, and living in Denmark. Cox proportional hazards analysis evaluating the effect of intravitreal VEGF inhibitory treatment on incident CVD and all-cause mortality. A predefined analysis plan specified primary outcomes as hazard ratios (HRs) of a composite CVD endpoint and all-cause mortality in patients treated with anti-VEGF compared with untreated. Secondary outcomes included cumulative dose analysis, HRs on subgroups of CVD, and stratified analyses evaluating the effect of sex, age, diabetes, intensive treatment, and preexisting CVD on the HRs. We found no increased risk of composite CVD (HR, 1.07; 95% confidence interval [CI], 0.89–1.29) or all-cause mortality (HR, 0.88; 95% CI, 0.77–1.00) in patients with RVO treated with anti-VEGF. In the secondary analyses, we found no dose-response relationship. We found an increased risk of intracranial hemorrhage (HR, 1.66; 95% CI, 1.02–2.71), but no increased risks in remaining subgroups of CVD. We found no increased risk associated with selected predisposing risk factors, and no increased risk in patients with preexisting CVD. 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Treatment with anti-VEGF in patients with RVO is safe, when evaluated in a nationwide, population-based setting. An increased risk of intracranial hemorrhage might be present, but cannot be reliably quantified and should be further elucidated by larger population-based studies including all indications for anti-VEGF treatment. 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subjects Cardiovascular diseases
Mortality
Retinal vein occlusion
Vascular endothelial growth factor inhibitors
title VEGF Inhibition in Retinal Vein Occlusion Does Not Associate with Cardiovascular Morbidity or Mortality
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