Cilostazol for DCI Prevention

Cilostazol is a phosphodiesterase III inhibitor which increases cAMP and leads to reversible inhibition of platelet aggregation, vasodilation and inhibition of vascular smooth muscle cell proliferation.  A systematic review was recently published in the Journal of Neurology on the effect of cilostazol on the incidence of delayed cerebral ischemia in subarachnoid hemorrhage (Department of Neurosurgery, West China Hospital).

The meta-analysis included seven studies, all of which were done in Japan:  three were randomized controlled studies, 3 were retrospective studies and one was a prospective study.  Most studies used cilostazol at 200mg per day for 14 days.

studies

Forest plots for the outcomes provided below:

A. Severe angiographic vasospasm

forest plot 1

B. Symptomatic vasospasm

forest plot 2

C. New cerebral infarction

forest plot 3

D. Poor outcome

forest plot 4

E.  Mortality

forest plot 5

Adverse effects related to cilostazol administration in the studies include diarrhea, transaminitis, tachycardia, headaches, hemorrhagic and cardiac events.

The meta-analysis concluded that cilostazol effectively reduced the incidence of severe angiographic vasospasm, symptomatic vasospasm, new cerebral infarction and poor outcome in patients with aneurysmal subarachnoid hemorrhage, but does not reduce mortality significantly.

It is important to note that all of the studies included in the meta-analysis were from one country (Japan), which precludes the generalization of the results to the general population.  Also, none of the patients in the studies received nimodipine, which has not been approved for SAH treatment in Japan.  Whether or not the co-administration of nimodipine would add to or nullify the benefits seen with cilostazol requires further investigation.

Take home message:  should not change current practice, needs further research.

 

References:

Shan, T., Zhang, T., Qian, W., Ma, L., Li, H., You, C. and Xie, X. (2019). Effectiveness and feasibility of cilostazol in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. Journal of Neurology.

Uptodate.com. (2019). UpToDate. [online] Available at: https://www.uptodate.com/contents/cilostazol-drug-information?sectionName=Adult&topicId=8872&search=cilostazol&usage_type=panel&anchor=F151445&source=panel_search_result&selectedTitle=1~36&kp_tab=drug_general&display_rank=1#F151413 [Accessed 6 Apr. 2019].

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