Dose-Dependent Inhibitory Effects of Cilostazol on Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage
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Cilostazol is a selective inhibitor of phosphodiesterase type III that downregulates tenascin-C (TNC), a matricellular protein, which may cause delayed cerebral infarction after aneurysmal subarachnoid hemorrhage (SAH). The authors increased the dosage and evaluated the dose-dependent effects of cilostazol on delayed cerebral infarction and outcomes in SAH patients. This was a retrospective cohort study in a single center. One hundred fifty-six consecutive SAH patients including 67 patients of admission World Federation of Neurological Surgeons grades IV–V who underwent aneurysmal obliteration within 48 h post-SAH from 2007 to 2017 were analyzed. Cilostazol (0 to 300 mg/day) was administered from 1-day post-clipping or post-coiling to day 14 or later. Cilostazol treatment dose-dependently decreased delayed cerebral infarction and tended to improve outcomes, although cilostazol did not affect other outcome measures including angiographic vasospasm. On multivariate analyses, 300 mg/day (100 mg three times) cilostazol independently decreased delayed cerebral infarction and improved 3-month outcomes, but other regimens including 200 mg/day (100 mg twice) cilostazol were not independent prognostic factors. Propensity score-matched analyses showed that the 300 mg/day cilostazol cohort had lower plasma TNC levels and a lower incidence of delayed cerebral infarction associated with better outcomes compared with the non-cilostazol cohort. The 300 mg/day cilostazol may improve post-SAH outcomes by reducing plasma TNC levels and delayed cerebral infarction, but not vasospasm. Further studies are warranted to investigate if 300 mg/day cilostazol is more beneficial to post-SAH outcomes than a usual dose of 200 mg/day cilostazol that was demonstrated to be effective in randomized controlled trials.
KeywordsCerebral infarction Cerebral vasospasm Cilostazol Delayed cerebral ischemia Subarachnoid hemorrhage Tenascin-C
We thank Ms. Chiduru Yamamoto (Department of Neurosurgery, Mie University Graduate School of Medicine) for her technical assistance.
This work was funded by a grant-in-aid for Scientific Research from Japan Society for the Promotion of Science (grant number 17K10825) to Dr. Suzuki.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
This article does not contain any studies with animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study as to TNC measurements. For other retrospective analyses, formal consent is not required.
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