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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

Authors

Caroline McHutchison

Gordon W Blair

Jason P Appleton

Francesca M Chappell

Fergus Doubal

PHILIP BATH philip.bath@nottingham.ac.uk
Stroke Association Professor of Stroke Medicine

Joanna M Wardlaw joanna.wardlaw@ed.ac.uk



Abstract

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 stabilises endothelium, aids myelin repair and astrocyte-neuron energy transfer in laboratory models, effects that may be beneficial in preventing small vessel disease (SVD) progression. Methods: A systematic review and meta-analysis of unconfounded randomised controlled trials (RCTs) of cilostazol to prevent stroke, cognitive decline or radiological SVD lesion progression. Two reviewers searched for papers (01/01/19-16/07/19) and extracted data. We calculated Peto odds ratios (OR) and 95% confidence intervals (CI) for recurrent ischaemic, haemorrhagic stroke, death, adverse symptoms, with sensitivity analyses. The review is registered (CRD42018084742). Results: We included 20 RCTs (n=10505), 18 in ischaemic stroke (total n=10449) and two in cognitive impairment (n= 56); most were performed in Asia-Pacific countries. Cilostazol decreased recurrent ischaemic stroke (17 trials, n=10225, OR=0.68, 95%CI=0.57 to 0.81, P40%) 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 haemorrhage 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 SVD.

Citation

McHutchison, C., Blair, G. W., Appleton, J. P., Chappell, F. M., Doubal, F., Bath, P. M., & Wardlaw, J. M. (2020). Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis. Stroke, 51(8), 2374-2385. https://doi.org/10.1161/strokeaha.120.029454

Journal Article Type Article
Acceptance Date Jun 6, 2020
Online Publication Date Jul 10, 2020
Publication Date 2020-08
Deposit Date Jun 19, 2020
Publicly Available Date Jan 11, 2021
Journal Stroke
Print ISSN 0039-2499
Electronic ISSN 1524-4628
Publisher American Heart Association
Peer Reviewed Peer Reviewed
Volume 51
Issue 8
Pages 2374-2385
DOI https://doi.org/10.1161/strokeaha.120.029454
Keywords cilostazol; stroke; systematic review
Public URL https://nottingham-repository.worktribe.com/output/4667871
Publisher URL https://www.ahajournals.org/doi/10.1161/STROKEAHA.120.029454