Vascular toxicities with VEGF inhibitor therapies–focus on hypertension and arterial thrombotic events

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19 Citations (Scopus)

Abstract

The vascular endothelial growth factor (VEGF) signaling pathway (VSP) fulfills a cardinal role in endothelial cells and its inhibition has profound cardiovascular impact. This is true not only for the normal vasculature but also for the tumor vasculature when VSP inhibitors are used as anti-angiogenic therapies. Generalized endothelial dysfunction predisposes to vasoconstriction, atherosclerosis, platelet activation, and thrombosis (arterial more than venous). All of these have been reported with VSP inhibitors and collectively give rise to vascular toxicities, the most concerning of which are arterial thromboembolic events (ATE). VSP inhibitors include antibodies, acting extracelluarly on VEGF, such as bevacizumab and tyrosine kinases inhibitors, acting intracellularly on the kinase domain of VEGF receptors, such as sunintib and sorafenib. The addition of bevacizumab and VSP tyrosine kinase inhibitor therapy to the cancer treatment regimen is associated with a 1.5–2.5-fold and 2.3–4.6-fold increase risk of ATEs, respectively. Risk factors for ATEs while on VSP inhibitor therapy include age older than 65 years, previous thromboembolic events, history of atherosclerotic disease, and duration of VSP inhibitor therapy. In clinical practice, hypertension remains the most commonly noted vascular manifestation of VSP inhibition. Optimal blood pressure goals and preferred therapeutic strategies toward reaching these goals are not defined at present. This review summarizes current data on this topic and proposes a more intensive management approach to patients undergoing VSP inhibitor therapy including Systolic Blood PRessure Intervention Trial (SPRINT) blood pressure goals, pleiotropic vasoprotective agents such as angiotensin converting enzyme inhibitors, amlodipine, and carvedilol, high-dose statin therapy, and aspirin.

Original languageEnglish (US)
Pages (from-to)409-425
Number of pages17
JournalJournal of the American Society of Hypertension
Volume12
Issue number6
DOIs
StatePublished - Jun 1 2018

Fingerprint

Vascular Endothelial Growth Factor A
Blood Vessels
Hypertension
Blood Pressure
Therapeutics
Protein-Tyrosine Kinases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Amlodipine
Vascular Endothelial Growth Factor Receptor
Platelet Activation
Vasoconstriction
Angiotensin-Converting Enzyme Inhibitors
Aspirin
Neoplasms
Atherosclerosis
Thrombosis
Phosphotransferases
Endothelial Cells
Antibodies

Keywords

  • Angiogenesis inhibitors
  • cardiovascular events
  • chemotherapy
  • hypertension

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Vascular toxicities with VEGF inhibitor therapies–focus on hypertension and arterial thrombotic events",
abstract = "The vascular endothelial growth factor (VEGF) signaling pathway (VSP) fulfills a cardinal role in endothelial cells and its inhibition has profound cardiovascular impact. This is true not only for the normal vasculature but also for the tumor vasculature when VSP inhibitors are used as anti-angiogenic therapies. Generalized endothelial dysfunction predisposes to vasoconstriction, atherosclerosis, platelet activation, and thrombosis (arterial more than venous). All of these have been reported with VSP inhibitors and collectively give rise to vascular toxicities, the most concerning of which are arterial thromboembolic events (ATE). VSP inhibitors include antibodies, acting extracelluarly on VEGF, such as bevacizumab and tyrosine kinases inhibitors, acting intracellularly on the kinase domain of VEGF receptors, such as sunintib and sorafenib. The addition of bevacizumab and VSP tyrosine kinase inhibitor therapy to the cancer treatment regimen is associated with a 1.5–2.5-fold and 2.3–4.6-fold increase risk of ATEs, respectively. Risk factors for ATEs while on VSP inhibitor therapy include age older than 65 years, previous thromboembolic events, history of atherosclerotic disease, and duration of VSP inhibitor therapy. In clinical practice, hypertension remains the most commonly noted vascular manifestation of VSP inhibition. Optimal blood pressure goals and preferred therapeutic strategies toward reaching these goals are not defined at present. This review summarizes current data on this topic and proposes a more intensive management approach to patients undergoing VSP inhibitor therapy including Systolic Blood PRessure Intervention Trial (SPRINT) blood pressure goals, pleiotropic vasoprotective agents such as angiotensin converting enzyme inhibitors, amlodipine, and carvedilol, high-dose statin therapy, and aspirin.",
keywords = "Angiogenesis inhibitors, cardiovascular events, chemotherapy, hypertension",
author = "Touyz, {Rhian M.} and Sandra Herrmann and Joerg Herrmann",
year = "2018",
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TY - JOUR

T1 - Vascular toxicities with VEGF inhibitor therapies–focus on hypertension and arterial thrombotic events

AU - Touyz, Rhian M.

AU - Herrmann, Sandra

AU - Herrmann, Joerg

PY - 2018/6/1

Y1 - 2018/6/1

N2 - The vascular endothelial growth factor (VEGF) signaling pathway (VSP) fulfills a cardinal role in endothelial cells and its inhibition has profound cardiovascular impact. This is true not only for the normal vasculature but also for the tumor vasculature when VSP inhibitors are used as anti-angiogenic therapies. Generalized endothelial dysfunction predisposes to vasoconstriction, atherosclerosis, platelet activation, and thrombosis (arterial more than venous). All of these have been reported with VSP inhibitors and collectively give rise to vascular toxicities, the most concerning of which are arterial thromboembolic events (ATE). VSP inhibitors include antibodies, acting extracelluarly on VEGF, such as bevacizumab and tyrosine kinases inhibitors, acting intracellularly on the kinase domain of VEGF receptors, such as sunintib and sorafenib. The addition of bevacizumab and VSP tyrosine kinase inhibitor therapy to the cancer treatment regimen is associated with a 1.5–2.5-fold and 2.3–4.6-fold increase risk of ATEs, respectively. Risk factors for ATEs while on VSP inhibitor therapy include age older than 65 years, previous thromboembolic events, history of atherosclerotic disease, and duration of VSP inhibitor therapy. In clinical practice, hypertension remains the most commonly noted vascular manifestation of VSP inhibition. Optimal blood pressure goals and preferred therapeutic strategies toward reaching these goals are not defined at present. This review summarizes current data on this topic and proposes a more intensive management approach to patients undergoing VSP inhibitor therapy including Systolic Blood PRessure Intervention Trial (SPRINT) blood pressure goals, pleiotropic vasoprotective agents such as angiotensin converting enzyme inhibitors, amlodipine, and carvedilol, high-dose statin therapy, and aspirin.

AB - The vascular endothelial growth factor (VEGF) signaling pathway (VSP) fulfills a cardinal role in endothelial cells and its inhibition has profound cardiovascular impact. This is true not only for the normal vasculature but also for the tumor vasculature when VSP inhibitors are used as anti-angiogenic therapies. Generalized endothelial dysfunction predisposes to vasoconstriction, atherosclerosis, platelet activation, and thrombosis (arterial more than venous). All of these have been reported with VSP inhibitors and collectively give rise to vascular toxicities, the most concerning of which are arterial thromboembolic events (ATE). VSP inhibitors include antibodies, acting extracelluarly on VEGF, such as bevacizumab and tyrosine kinases inhibitors, acting intracellularly on the kinase domain of VEGF receptors, such as sunintib and sorafenib. The addition of bevacizumab and VSP tyrosine kinase inhibitor therapy to the cancer treatment regimen is associated with a 1.5–2.5-fold and 2.3–4.6-fold increase risk of ATEs, respectively. Risk factors for ATEs while on VSP inhibitor therapy include age older than 65 years, previous thromboembolic events, history of atherosclerotic disease, and duration of VSP inhibitor therapy. In clinical practice, hypertension remains the most commonly noted vascular manifestation of VSP inhibition. Optimal blood pressure goals and preferred therapeutic strategies toward reaching these goals are not defined at present. This review summarizes current data on this topic and proposes a more intensive management approach to patients undergoing VSP inhibitor therapy including Systolic Blood PRessure Intervention Trial (SPRINT) blood pressure goals, pleiotropic vasoprotective agents such as angiotensin converting enzyme inhibitors, amlodipine, and carvedilol, high-dose statin therapy, and aspirin.

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U2 - 10.1016/j.jash.2018.03.008

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