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Long-term effectiveness and safety of cilostazol versus clopidogrel in secondary prevention of noncardioembolic ischemic stroke

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Abstract

Purpose

Cilostazol is a widely used antiplatelet drug for secondary stroke prevention in Asia, but its comparison with clopidogrel is not well understood. This study aims to investigate the effectiveness and safety of cilostazol compared to clopidogrel for the secondary prevention of noncardioembolic ischemic stroke.

Methods

This retrospective comparative effectiveness research analyzed 1:1 propensity scorematched data from insured individuals between 2012 and 2019, using administrative claims data in Health Insurance Review and Assessment in Korea. Patients with diagnosis codes for ischemic stroke without cardiac disease were included and divided into two groups, those receiving cilostazol and those receiving clopidogrel. The primary outcome was a recurrent ischemic stroke. Secondary outcomes included all-cause death, myocardial infarction, hemorrhagic stroke, and a composite of these outcomes. The safety outcome was major gastrointestinal bleeding.

Results

The study analyzed 4,754 patients in the propensity scorematched population and found no statistically significant difference in recurrent ischemic stroke (cilostazol group vs clopidogrel group, 2.7% vs 3.2%; 95% CI, 0.62–1.21), the composite outcome of recurrent ischemic stroke, all-cause death, myocardial infarction, and hemorrhagic stroke (5.1% vs 5.5%; 0.75–1.22), and major gastrointestinal bleeding (1.3% vs 1.5%; 0.57–1.47) between patients receiving cilostazol and those receiving clopidogrel. In subgroup analysis, cilostazol was associated with a lower incidence of recurrent ischemic stroke compared to clopidogrel in hypertensive patients (2.5% vs 3.9%; interaction P = 0.041).

Conclusions

This real-world study suggests that cilostazol is effective and safe for noncardioembolic ischemic stroke and may be associated with better effectiveness in hypertensive patients compared to clopidogrel.

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Data availability

The authors used the HIRA research database (M20220628003) for this study and do not have permission to share these data. Raw data can be accessed with permission from Health Insurance Review and Assessment Service in Korea (http://opendata.hira.or.kr).

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Funding

No funding was received for conducting this study.

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Authors and Affiliations

  1. College of Pharmacy, Pusan National University, Busan, Republic of Korea

    Yu Jeong Lee & Nam Kyung Je

  2. Department of Pharmacy, Pusan National University Hospital, Busan, Republic of Korea

    Yu Jeong Lee

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Contributions

Yu Jeong Lee and Nam Kyung Je contributed to the study conception and design. Data analysis were performed by Yu Jeong Lee. The first draft of the manuscript was written by Yu Jeong Lee. Yu Jeong Lee and Nam Kyung Je participated in drafting the article and approved the final manuscript to be submitted for publication.

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Correspondence to Nam Kyung Je.

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All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.

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Ethical approval was waived by the institutional review board of the Pusan national university (No. PNU IRB/2022_114_HR) in view of the retrospective nature of the study and all the procedures being performed were part of the routine care.

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Lee, Y.J., Je, N.K. Long-term effectiveness and safety of cilostazol versus clopidogrel in secondary prevention of noncardioembolic ischemic stroke. Eur J Clin Pharmacol 79, 1107–1116 (2023). https://doi.org/10.1007/s00228-023-03522-3

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