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Cilostazol for secondary stroke prevention: systematic review and meta-analysis
  1. Choon Han Tan1,
  2. Andrew GR Wu2,
  3. Ching-Hui Sia3,
  4. Aloysius ST Leow4,
  5. Bernard PL Chan4,
  6. Vijay Kumar Sharma2,4,
  7. Leonard LL Yeo2,4,
  8. Benjamin YQ Tan2,4
  1. 1 Department of Medicine, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
  2. 2 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  3. 3 Department of Cardiology, National University Heart Centre, Singapore
  4. 4 Division of Neurology, Department of Medicine, National University Health System, Singapore
  1. Correspondence to Dr Leonard LL Yeo; leonard_ll_yeo{at}nuhs.edu.sg

Abstract

Background Stroke is one of the leading causes of death worldwide. Cilostazol, an antiplatelet and phosphodiesterase 3 inhibitor, has not been clearly established for ischaemic stroke use. We aim to determine the efficacy and safety of cilostazol for secondary stroke prevention.

Methods MEDLINE, EMBASE, Cochrane Library, Web of Science and ClinicalTrials.gov were searched from inception to 25 September 2020, for randomised trials comparing the efficacy and safety of cilostazol monotherapy or dual therapy with another antiplatelet regimen or placebo, in patients with ischaemic stroke. Version 2 of the Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to assess study quality. This meta-analysis was reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Results Eighteen randomised trials comprising 11 429 participants were included in this meta-analysis. Most trials possessed low risk of bias and were of low heterogeneity. Cilostazol significantly reduced the rate of ischaemic stroke recurrence (risk ratio, RR=0.69, 95% CI 0.58 to 0.81), any stroke recurrence (RR=0.64, 95% CI 0.54 to 0.74) and major adverse cardiovascular events (RR=0.67, 95% CI 0.56 to 0.81). Cilostazol did not significantly decrease mortality (RR=0.90, 95% CI 0.64 to 1.25) or increase the rate of good functional outcome (Modified Rankin Scale score of 0–1; RR=1.07, 95% CI 0.95 to 1.19). Cilostazol demonstrated favourable safety profile, significantly reducing the risk of intracranial haemorrhage (RR=0.46, 95% CI 0.31 to 0.68) and major haemorrhagic events (RR=0.49, 95% CI 0.34 to 0.70).

Conclusions Cilostazol demonstrated superior efficacy and safety profiles compared with traditional antiplatelet regimens such as aspirin and clopidogrel for secondary stroke prevention but does not appear to affect functional outcomes. Future randomised trials can be conducted outside East Asia, or compare cilostazol with a wider range of antiplatelet agents.

  • stroke
  • haemorrhage
  • platelets
  • stenosis

Data availability statement

Data are available upon reasonable request.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/svn-2020-000737

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    Data availability statement

    Data are available upon reasonable request.

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    Footnotes

    • CHT and AGW are joint first authors.

    • Contributors All coauthors made significant contributions to the planning, conduct, reporting and final approval of the study. CHT and AGRW are co-first authors.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.