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

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