Introduction: Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) is a major cause of subsequent morbidity and mortality. Cilostazol, a selective inhibitor of phosphodiesterase 3, may attenuate cerebral vasospasm because of its antiplatelet and vasodilatory effects. A multicenter prospective randomized trial was conducted to investigate the effect of cilostazol on cerebral vasospasm.
Methods: Patients who admitted with SAH caused by ruptured anterior circulation aneurysm in Hunt and Kosnik grades I to IV and treated by clipping were enrolled at 7 neurosurgical sites in Japan, and randomly allocated to the usual therapy group (control group) or the add-on cilostazol 100mg twice daily group (cilostazol group). Primary endpoint was the onset of symptomatic vasospasm. Secondary endpoints were the onset of angiographic vasospasm as well as new cerebral infarctions related with cerebral vasospasm, clinical outcome assessed by the modified Rankin scale and length of hospitalization. All endpoints were assessed for the intention-to-treat population.
Results: From November 2009 to December 2010, 109 patients were randomly allocated to the cilostazol group (n= 54) or the control groups (n= 55). Symptomatic vasospasm occurred in 13% of the cilostazol group and in 40% of the control group (p=0.0021). The incidence of angiographic vasospasm was significantly lower in the cilostazol group than the control group (50% versus 77% respectively; p=0.0055). The incidence of new cerebral infarctions was also significantly lower in the cilostazol group than the control group (11% versus 29% respectively; p=0.0304). Clinical outcomes at 1, 3 and 6 months after SAH of the cilostazol group was better than that of the control group, although significant difference was not shown. There was also no significant difference in the length of hospitalization between the groups. No severe adverse event occurred during the study period.
Conclusions: Oral administration of cilostazol is effective to prevent cerebral vasospasm with a low risk of severe adverse events.
Patient Care: Cilostazol prevents cerebral vasospasm after SAH and may have the potential to lead improvement of final outcome after aneurysmal SAH.
Learning Objectives: By the conclusion of this session, participants should be able to identify cilostazol effect on cerebral vasospasm following SAH.