Cilostazol for the Management of Moyamoya Disease: Current Evidence, Gaps, and Clinical Implications

Introduction: Surgical revascularization remains the standard treatment for symptomatic moyamoya disease (MMD). As with any major surgical treatment, revascularization is associated with risks and limitations, denoting the need for non-invasive treatments to improve ischemic symptoms and prevent stroke. Cilostazol is a selective phosphodiesterase-III inhibitor with antiplatelet, antithrombotic, and vasodilatory effects commonly used in peripheral vascular disease. Clinical studies assessing the efficacy of cilostazol in managing stroke and now MMD have recently emerged, although a comprehensive assessment of the overall evidence is lacking.

Methods: PubMed and ClinicalTrials.gov were queried for studies on the use, efficacy, and safety of cilostazol in MMD. Meta-analysis was planned, however, was not performed due to the scarcity of sufficiently homogeneous studies. The literature was critically appraised, and the clinical implications and limitations are reviewed and discussed.

Results: East Asian studies demonstrate increasing rates of cilostazol prescriptions for patients with MMD. In a large population-based study, cilostazol was compared to other antiplatelet medications and yielded the largest decrease in mortality among patients with newly-diagnosed MMD. Other studies reported significant improvements in cerebral blood flow and cognitive function, which were deemed to be independent of one another. There is limited data on the safety profile of cilostazol in MMD, although the evidence derived from various studies performed in the general stroke population can be adapted to MMD patients.

Conclusion : Cilostazol targets several critical pathways involved in the pathophysiology of MMD. The evidence corroborates the benefits of cilostazol for management of MMD, although these findings should be interpreted with caution due to the small number of studies and lack of randomized trials. Subgroups of patients need to be identified who can safely undergo medical management in lieu of revascularization surgery or to improve its outcomes. Additional studies are needed to assess the efficacy and safety of cilostazol therapy, especially in Western populations.