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

Touyz, R. M. , Herrmann, S. M.S. and Herrmann, J. (2018) Vascular toxicities with VEGF inhibitor therapies-focus on hypertension and arterial thrombotic events. Journal of the American Society of Hypertension, 12(6), pp. 409-425. (doi: 10.1016/j.jash.2018.03.008) (PMID:29703600) (PMCID:PMC6168784)

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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.

Item Type:Articles
Keywords:Angiogenesis inhibitors, cardiovascular events, chemotherapy, hypertension.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Touyz, R. M., Herrmann, S. M.S., and Herrmann, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of the American Society of Hypertension
Publisher:Elsevier
ISSN:1933-1711
ISSN (Online):1878-7436
Published Online:21 March 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Journal of the American Society of Hypertension 12(6): 409-425
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
607381Vascular Noxs as therapeutic targets and biomarkers in hypertensionRhian TouyzBritish Heart Foundation (BHF)CH/12/4/29762RI CARDIOVASCULAR & MEDICAL SCIENCES