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

• DOI: 10.1007/s12975-018-0650-y
• Publication Date: 2018-07-22T23:28:26Z
• Authors: Hidenori Suzuki; Yoshinari Nakatsuka; Ryuta Yasuda; Masato Shiba; Yoichi Miura; Mio Terashima; Yume Suzuki; Koichi Hakozaki; Fuki Goto; Naoki Toma
• Keywords: Adult; Aged, 80 and over; Male; Time Factors; Dose-Response Relationship, Drug; Cerebral Infarction; Middle Aged; Subarachnoid Hemorrhage; Phosphodiesterase 3 Inhibitors; Cilostazol; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Humans; Female; Prospective Studies; Aged; Retrospective Studies

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.