Pharmacological treatment and prevention of cerebral small vessel disease: a review of potential interventions

Small vessel disease encompasses lacunar stroke, white matter hyperintensities, lacunes and microbleeds. It causes a quarter of all ischemic strokes, is the commonest cause of vascular dementia, and the cause is incompletely understood. Vascular prophylaxis, as appropriate for large artery disease a...

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Main Authors: Bath, Philip M.W., Wardlaw, Joanna M.
Format: Article
Published: SAGE 2015
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Online Access:https://eprints.nottingham.ac.uk/35712/
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author Bath, Philip M.W.
Wardlaw, Joanna M.
author_facet Bath, Philip M.W.
Wardlaw, Joanna M.
author_sort Bath, Philip M.W.
building Nottingham Research Data Repository
collection Online Access
description Small vessel disease encompasses lacunar stroke, white matter hyperintensities, lacunes and microbleeds. It causes a quarter of all ischemic strokes, is the commonest cause of vascular dementia, and the cause is incompletely understood. Vascular prophylaxis, as appropriate for large artery disease and cardioembolism, includes antithrombotics, and blood pressure and lipid lowering; however, these strategies may not be effective for small vessel disease, or are already used routinely so precluding further detailed study. Further, intensive antiplatelet therapy is known to be hazardous in small vessel disease through enhanced bleeding. Whether acetylcholinesterase inhibitors, which delay the progression of Alzheimer's dementia, are relevant in small vessel disease remains unclear. Potential prophylactic and treatment strategies might be those that target brain microvascular endothelium and the blood brain barrier, microvascular function and neuroinflammation. Potential interventions include endothelin antagonists, neurotrophins, nitric oxide donors and phosphodiesterase 5 inhibitors, peroxisome proliferator-activated receptor-gamma agonists, and prostacyclin mimics and phosphodiesterase 3 inhibitors. Several drugs that have relevant properties are licensed for other disorders, offering the possibility of drug repurposing. Others are in development. Since influencing multiple targets may be most effective, using multiple agents and/or those that have multiple effects may be preferable. We focus on potential small vessel disease mechanistic targets, summarize drugs that have relevant actions, and review data available from randomized trials on their actions and on the available evidence for their use in lacunar stroke.
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spelling nottingham-357122020-05-04T20:08:22Z https://eprints.nottingham.ac.uk/35712/ Pharmacological treatment and prevention of cerebral small vessel disease: a review of potential interventions Bath, Philip M.W. Wardlaw, Joanna M. Small vessel disease encompasses lacunar stroke, white matter hyperintensities, lacunes and microbleeds. It causes a quarter of all ischemic strokes, is the commonest cause of vascular dementia, and the cause is incompletely understood. Vascular prophylaxis, as appropriate for large artery disease and cardioembolism, includes antithrombotics, and blood pressure and lipid lowering; however, these strategies may not be effective for small vessel disease, or are already used routinely so precluding further detailed study. Further, intensive antiplatelet therapy is known to be hazardous in small vessel disease through enhanced bleeding. Whether acetylcholinesterase inhibitors, which delay the progression of Alzheimer's dementia, are relevant in small vessel disease remains unclear. Potential prophylactic and treatment strategies might be those that target brain microvascular endothelium and the blood brain barrier, microvascular function and neuroinflammation. Potential interventions include endothelin antagonists, neurotrophins, nitric oxide donors and phosphodiesterase 5 inhibitors, peroxisome proliferator-activated receptor-gamma agonists, and prostacyclin mimics and phosphodiesterase 3 inhibitors. Several drugs that have relevant properties are licensed for other disorders, offering the possibility of drug repurposing. Others are in development. Since influencing multiple targets may be most effective, using multiple agents and/or those that have multiple effects may be preferable. We focus on potential small vessel disease mechanistic targets, summarize drugs that have relevant actions, and review data available from randomized trials on their actions and on the available evidence for their use in lacunar stroke. SAGE 2015-06 Article PeerReviewed Bath, Philip M.W. and Wardlaw, Joanna M. (2015) Pharmacological treatment and prevention of cerebral small vessel disease: a review of potential interventions. International Journal of Stroke, 10 (4). pp. 469-478. ISSN 1747-4949 antithrombotics blood brain barrier blood pressure lowering cyclic nucleotide inhibitors nitric oxide prostacyclin http://onlinelibrary.wiley.com/doi/10.1111/ijs.12466/abstract doi:10.1111/ijs.12466 doi:10.1111/ijs.12466
spellingShingle antithrombotics
blood brain barrier
blood pressure lowering
cyclic nucleotide inhibitors
nitric oxide
prostacyclin
Bath, Philip M.W.
Wardlaw, Joanna M.
Pharmacological treatment and prevention of cerebral small vessel disease: a review of potential interventions
title Pharmacological treatment and prevention of cerebral small vessel disease: a review of potential interventions
title_full Pharmacological treatment and prevention of cerebral small vessel disease: a review of potential interventions
title_fullStr Pharmacological treatment and prevention of cerebral small vessel disease: a review of potential interventions
title_full_unstemmed Pharmacological treatment and prevention of cerebral small vessel disease: a review of potential interventions
title_short Pharmacological treatment and prevention of cerebral small vessel disease: a review of potential interventions
title_sort pharmacological treatment and prevention of cerebral small vessel disease: a review of potential interventions
topic antithrombotics
blood brain barrier
blood pressure lowering
cyclic nucleotide inhibitors
nitric oxide
prostacyclin
url https://eprints.nottingham.ac.uk/35712/
https://eprints.nottingham.ac.uk/35712/
https://eprints.nottingham.ac.uk/35712/