Anti-VEGF agents and the risk of arteriothrombotic events

Research output: Contribution to journalReview article

11 Citations (Scopus)

Abstract

Blockade of vascular endothelial growth factor (VEGF) signaling, whether via sequestration of free VEGF or via inhibition of the tyrosine kinases activated by VEGF, is associated with decreased nitric oxide (NO) and prostaglandin-I 2 (PG-I 2) production along with vascular endothelial cell death. Systemic administration of drugs that block VEGF signaling (eg, for cancer treatment) is associated with systemic complications such as hypertension and thrombosis. Evidence regarding the risk of systemic serious adverse events after intravitreal injection of anti-VEGF agents in patients with diabetic macular edema or neovascular age-related macular degeneration is inconsistent, in part because of study design limitations (eg, bias of ascertainment through strict enrollment criteria and/or inadequate power to identify the risk of low frequency events). Studies involving patients at high risk of arteriothrombotic events (eg, patients with diabetic macular edema) who have high exposure to intra-vitreal anti-VEGF therapy (eg, monthly aflibercept or ranibizumab injection) demonstrate an increased risk of all-cause mortality compared with randomized controls. The pharmacokinetics of anti-VEGF drug clearance from the systemic circulation and the documented sustained reduction in free plasma VEGF levels after intravitreal aflibercept and bevacizumab injection are consistent with these findings. Although the frequency of systemic serious adverse events after intravitreal anti-VEGF therapy is low, some patients may be at higher risk (eg, those with recent stroke or multiple strokes), and physicians may wish to take special measures with these patients to minimize the risk of systemic complications.

Original languageEnglish (US)
Pages (from-to)63-67
Number of pages5
JournalAsia-Pacific Journal of Ophthalmology
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Vascular Endothelial Growth Factor A
Macular Edema
Stroke
Intravitreal Injections
Injections
Second Primary Neoplasms
Macular Degeneration
Proxy
Epoprostenol
Pharmaceutical Preparations
Protein-Tyrosine Kinases
Nitric Oxide
Thrombosis
Cell Death
Endothelial Cells
Pharmacokinetics
Hypertension
Physicians
Mortality
Therapeutics

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Keywords

  • Anti-VEGF agents
  • Arteriothrombotic events
  • Plausibility

Cite this

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title = "Anti-VEGF agents and the risk of arteriothrombotic events",
abstract = "Blockade of vascular endothelial growth factor (VEGF) signaling, whether via sequestration of free VEGF or via inhibition of the tyrosine kinases activated by VEGF, is associated with decreased nitric oxide (NO) and prostaglandin-I 2 (PG-I 2) production along with vascular endothelial cell death. Systemic administration of drugs that block VEGF signaling (eg, for cancer treatment) is associated with systemic complications such as hypertension and thrombosis. Evidence regarding the risk of systemic serious adverse events after intravitreal injection of anti-VEGF agents in patients with diabetic macular edema or neovascular age-related macular degeneration is inconsistent, in part because of study design limitations (eg, bias of ascertainment through strict enrollment criteria and/or inadequate power to identify the risk of low frequency events). Studies involving patients at high risk of arteriothrombotic events (eg, patients with diabetic macular edema) who have high exposure to intra-vitreal anti-VEGF therapy (eg, monthly aflibercept or ranibizumab injection) demonstrate an increased risk of all-cause mortality compared with randomized controls. The pharmacokinetics of anti-VEGF drug clearance from the systemic circulation and the documented sustained reduction in free plasma VEGF levels after intravitreal aflibercept and bevacizumab injection are consistent with these findings. Although the frequency of systemic serious adverse events after intravitreal anti-VEGF therapy is low, some patients may be at higher risk (eg, those with recent stroke or multiple strokes), and physicians may wish to take special measures with these patients to minimize the risk of systemic complications.",
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Anti-VEGF agents and the risk of arteriothrombotic events. / Zarbin, Marco.

In: Asia-Pacific Journal of Ophthalmology, Vol. 7, No. 1, 01.01.2018, p. 63-67.

Research output: Contribution to journalReview article

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