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Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis
BACKGROUND AND PURPOSE: Cilostazol, a phosphodiesterase 3’ inhibitor, is used in Asia-Pacific countries for stroke prevention, but rarely used elsewhere. In addition to weak antiplatelet effects, it stabilizes endothelium, aids myelin repair and astrocyte-neuron energy transfer in laboratory models,...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382534/ https://www.ncbi.nlm.nih.gov/pubmed/32646330 http://dx.doi.org/10.1161/STROKEAHA.120.029454 |
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author | McHutchison, Caroline Blair, Gordon W. Appleton, Jason P. Chappell, Francesca M. Doubal, Fergus Bath, Philip M. Wardlaw, Joanna M. |
author_facet | McHutchison, Caroline Blair, Gordon W. Appleton, Jason P. Chappell, Francesca M. Doubal, Fergus Bath, Philip M. Wardlaw, Joanna M. |
author_sort | McHutchison, Caroline |
collection | PubMed |
description | BACKGROUND AND PURPOSE: Cilostazol, a phosphodiesterase 3’ inhibitor, is used in Asia-Pacific countries for stroke prevention, but rarely used elsewhere. In addition to weak antiplatelet effects, it stabilizes endothelium, aids myelin repair and astrocyte-neuron energy transfer in laboratory models, effects that may be beneficial in preventing small vessel disease progression. METHODS: A systematic review and meta-analysis of unconfounded randomized controlled trials of cilostazol to prevent stroke, cognitive decline, or radiological small vessel disease lesion progression. Two reviewers searched for papers (January 1, 2019 to July 16, 2019) and extracted data. We calculated Peto odds ratios (ORs) and 95% CIs for recurrent ischemic, hemorrhagic stroke, death, adverse symptoms, with sensitivity analyses. The review is registered (CRD42018084742). RESULTS: We included 20 randomized controlled trials (n=10 505), 18 in ischemic stroke (total n=10 449) and 2 in cognitive impairment (n=56); most were performed in Asia-Pacific countries. Cilostazol decreased recurrent ischemic stroke (17 trials, n=10 225, OR=0.68 [95% CI, 0.57–0.81]; P<0.0001), hemorrhagic stroke (16 trials, n=9736, OR=0.43 [95% CI, 0.29–0.64]; P=0.0001), deaths (OR=0.64 [95% CI, 0.49–0.83], P<0.0009), systemic bleeding (n=8387, OR=0.73 [95% CI, 0.54–0.99]; P=0.04), but increased headache and palpitations, compared with placebo, aspirin, or clopidogrel. Cilostazol reduced recurrent ischemic stroke more when given long (>6 months) versus short term without increasing hemorrhage, and in trials with larger proportions (>40%) of lacunar stroke. Data were insufficient to assess effects on cognition, imaging, functional outcomes, or tolerance. CONCLUSIONS: Cilostazol appears effective for long-term secondary stroke prevention without increasing hemorrhage risk. However, most trials related to Asia-Pacific patients and more trials in Western countries should assess its effects on cognitive decline, functional outcome, and tolerance, particularly in lacunar stroke and other presentations of small vessel disease. |
format | Online Article Text |
id | pubmed-7382534 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-73825342020-08-05 Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis McHutchison, Caroline Blair, Gordon W. Appleton, Jason P. Chappell, Francesca M. Doubal, Fergus Bath, Philip M. Wardlaw, Joanna M. Stroke Original Contributions BACKGROUND AND PURPOSE: Cilostazol, a phosphodiesterase 3’ inhibitor, is used in Asia-Pacific countries for stroke prevention, but rarely used elsewhere. In addition to weak antiplatelet effects, it stabilizes endothelium, aids myelin repair and astrocyte-neuron energy transfer in laboratory models, effects that may be beneficial in preventing small vessel disease progression. METHODS: A systematic review and meta-analysis of unconfounded randomized controlled trials of cilostazol to prevent stroke, cognitive decline, or radiological small vessel disease lesion progression. Two reviewers searched for papers (January 1, 2019 to July 16, 2019) and extracted data. We calculated Peto odds ratios (ORs) and 95% CIs for recurrent ischemic, hemorrhagic stroke, death, adverse symptoms, with sensitivity analyses. The review is registered (CRD42018084742). RESULTS: We included 20 randomized controlled trials (n=10 505), 18 in ischemic stroke (total n=10 449) and 2 in cognitive impairment (n=56); most were performed in Asia-Pacific countries. Cilostazol decreased recurrent ischemic stroke (17 trials, n=10 225, OR=0.68 [95% CI, 0.57–0.81]; P<0.0001), hemorrhagic stroke (16 trials, n=9736, OR=0.43 [95% CI, 0.29–0.64]; P=0.0001), deaths (OR=0.64 [95% CI, 0.49–0.83], P<0.0009), systemic bleeding (n=8387, OR=0.73 [95% CI, 0.54–0.99]; P=0.04), but increased headache and palpitations, compared with placebo, aspirin, or clopidogrel. Cilostazol reduced recurrent ischemic stroke more when given long (>6 months) versus short term without increasing hemorrhage, and in trials with larger proportions (>40%) of lacunar stroke. Data were insufficient to assess effects on cognition, imaging, functional outcomes, or tolerance. CONCLUSIONS: Cilostazol appears effective for long-term secondary stroke prevention without increasing hemorrhage risk. However, most trials related to Asia-Pacific patients and more trials in Western countries should assess its effects on cognitive decline, functional outcome, and tolerance, particularly in lacunar stroke and other presentations of small vessel disease. Lippincott Williams & Wilkins 2020-07-10 2020-08 /pmc/articles/PMC7382534/ /pubmed/32646330 http://dx.doi.org/10.1161/STROKEAHA.120.029454 Text en © 2020 The Authors. Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited. |
spellingShingle | Original Contributions McHutchison, Caroline Blair, Gordon W. Appleton, Jason P. Chappell, Francesca M. Doubal, Fergus Bath, Philip M. Wardlaw, Joanna M. Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis |
title | Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis |
title_full | Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis |
title_fullStr | Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis |
title_full_unstemmed | Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis |
title_short | Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis |
title_sort | cilostazol for secondary prevention of stroke and cognitive decline: systematic review and meta-analysis |
topic | Original Contributions |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382534/ https://www.ncbi.nlm.nih.gov/pubmed/32646330 http://dx.doi.org/10.1161/STROKEAHA.120.029454 |
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