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Effect of Cilostazol in Animal Models of Cerebral Ischemia and Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis

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An Invited Commentary to this article was published on 30 November 2022

Abstract

Background

Cilostazol, a phosphodiesterase III inhibitor, appears to be a promising agent for preventing cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage. Here, the authors perform a systematic review and meta-analysis to quantitatively assess the effects of cilostazol on brain structural and functional outcomes in animal models of cerebral ischemia and subarachnoid hemorrhage–induced cerebral vasospasm.

Methods

By using the PRISMA guidelines, a search of the PubMed, Scopus, and Web of Science was conducted to identify relevant studies. Study quality of each included study for both systematic reviews were scored by using an adapted 15-item checklist from the Collaborative Approach to Meta-Analysis of Animal Data from Experimental Studies. We calculated a standardized mean difference as effect size for each comparison. For each outcome, comparisons were combined by using random-effects modeling to account for heterogeneity, with a restricted maximum likelihood estimate of between-study variance.

Results

A total of 22 (median [Q1, Q3] quality score of 7 [5, 8]) and 6 (median [Q1, Q3] quality score of 6 [6, 6]) studies were identified for cerebral ischemia and subarachnoid hemorrhage–induced cerebral vasospasm, respectively. Cilostazol significantly reduced the infarct volume in cerebral ischemia models with a pooled standardized mean difference estimate of − 0.88 (95% confidence interval [CI] [− 1.07 to − 0.70], p < 0.0001). Cilostazol significantly reduced neurofunctional deficits in cerebral ischemia models with a pooled standardized mean difference estimate of − 0.66 (95% CI [− 1.06 to − 0.28], p < 0.0001). Cilostazol significantly improved the basilar artery diameter in subarachnoid hemorrhage–induced cerebral vasospasm with a pooled standardized mean difference estimate of 2.30 (95% CI [0.94 to 3.67], p = 0.001). Cilostazol also significantly improved the basilar artery cross-section area with a pooled standardized mean estimate of 1.88 (95% CI [0.33 to 3.43], p < 0.05). Overall, there was between-study heterogeneity and asymmetry in the funnel plot observed in all comparisons.

Conclusions

Published animal data support the overall efficacy of cilostazol in reducing infarct volume and neurofunctional deficits in cerebral ischemia models and cerebral vasospasm in subarachnoid hemorrhage models.

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Authors and Affiliations

  1. Department of Neurology, University of Missouri, Columbia, MO, USA

    Adnan I. Qureshi, Iqra N. Akhtar, Xiaoyu Ma, Abdullah Lodhi, Ibrahim Bhatti, Rishi Sharma & Mahesh Thakkar

  2. Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA

    Jonathan Beall, Christy N. Cassarly & Renee H. Martin

  3. Department of Neurology, University of Cincinnati, Cincinnati, OH, USA

    Joseph P. Broderick

  4. Division of Neurosciences Critical Care, Departments of Anesthesiology and Critical Care Medicine, Neurology, and Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jose I. Suarez

  5. Zeenat Qureshi Stroke Institute, St. Cloud, MN, USA

    Adnan I. Qureshi, Iqra N. Akhtar, Xiaoyu Ma, Abdullah Lodhi & Ibrahim Bhatti

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Contributions

AIQ: conception and design, acquisition of data, analysis and interpretation of data, drafting the article, critically revising the article, reviewed submitted version of manuscript, administrative/technical/material support, and study supervision. INA: conception and design, acquisition of data, analysis and interpretation of data, drafting the article, critically revising the article, and reviewed submitted version of manuscript. XM: statistical analysis, conception and design, acquisition of data, analysis and interpretation of data, drafting the article, critically revising the article, and reviewed submitted version of manuscript. AL: conception and design, acquisition of data, analysis and interpretation of data, drafting the article, critically revising the article, and reviewed submitted version of manuscript. IB: conception and design, acquisition of data, analysis and interpretation of data, drafting the article, critically revising the article, and reviewed submitted version of manuscript. JB: conception and design, acquisition of data, analysis and interpretation of data, drafting the article, critically revising the article, and reviewed submitted version of manuscript. JPB: conception and design, acquisition of data, analysis and interpretation of data, drafting the article, critically revising the article, and reviewed submitted version of manuscript. CNC: conception and design, acquisition of data, analysis and interpretation of data, drafting the article, critically revising the article, and reviewed submitted version of manuscript. RHM: conception and design, acquisition of data, analysis and interpretation of data, drafting the article, critically revising the article, and reviewed submitted version of manuscript. RS: conception and design, acquisition of data, analysis and interpretation of data, drafting the article, critically revising the article, and reviewed submitted version of manuscript. MT: conception and design, acquisition of data, analysis and interpretation of data, drafting the article, critically revising the article, and reviewed submitted version of manuscript. JIS: conception and design, acquisition of data, analysis and interpretation of data, drafting the article, critically revising the article, reviewed submitted version of manuscript, administrative/technical/material support, and study supervision. All authors approved the final manuscript prior to its submission.

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Correspondence to Adnan I. Qureshi.

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Qureshi, A.I., Akhtar, I.N., Ma, X. et al. Effect of Cilostazol in Animal Models of Cerebral Ischemia and Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis. Neurocrit Care 38, 698–713 (2023). https://doi.org/10.1007/s12028-022-01637-6

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