Dose-Dependent Inhibitory Effects of Cilostazol on Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage.

Abstract

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.

• Authors: Hidenori Suzuki, Yoshinari Nakatsuka, Ryuta Yasuda, Masato Shiba, Yoichi Miura, Mio Terashima, Yume Suzuki, Koichi Hakozaki, Fuki Goto, Naoki Toma
• Journal: Translational stroke research (Transl Stroke Res) Vol. 10 Issue 4 Pg. 381-388 (08 2019) ISSN: 1868-601X [Electronic] United States
• PMID: 30033486 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Phosphodiesterase 3 Inhibitors
• Cilostazol

Topics

• Adult
• Aged
• Aged, 80 and over
• Cerebral Infarction (diagnostic imaging, drug therapy, etiology)
• Cilostazol (therapeutic use)
• Dose-Response Relationship, Drug
• Female
• Humans
• Male
• Middle Aged
• Phosphodiesterase 3 Inhibitors (therapeutic use)
• Prospective Studies
• Retrospective Studies
• Subarachnoid Hemorrhage (complications, diagnostic imaging, drug therapy)
• Time Factors