Cilostazol in secondary prevention of stroke: impact of the Cilostazol Stroke Prevention Study.

According to recent epidemiological data in Japan, stroke affects roughly 5.3 males and 3.9 females per 1000 person-years and is the third leading cause of mortality. At present, management strategies for secondary prevention of stroke include aggressive treatment of cardiovascular risk factors (i.e., hypertension, smoking cessation, etc.). Antiplatelet drugs in Japan, namely aspirin and cilostazol, are utilized regularly for the prevention of secondary stroke. While aspirin is beneficial for a wide range of cardiovascular endpoints, including total and ischemic strokes, it is also associated with significantly increased risks for hemorrhagic infarction. Cilostazol, by contrast, has been shown to significantly reduce the risk of recurrent strokes without affecting the occurrence of intracranial hemorrhage. In the Cilostazol Stroke Prevention Study, a randomized double-blind, placebo-controlled trial involving more than 1000 Japanese patients, cilostazol was found to reduce the risk of secondary stroke by 41.7% compared with placebo, a statistically significant reduction (P = 0.015). The greatest risk reduction (43.4% in cilostazol versus placebo, P = 0.0373) was found in patients who initially had a lacunar infarction, suggesting that cilostazol has a specific effect against small-vessel disease. In addition, cilostazol achieved significant risk reductions on a number of combined endpoints (e.g., cerebral infarction, intracranial hemorrhage, myocardial infarction, or vascular death), and was associated with benefits in intent-to-treat analyses. These findings indicate that cilostazol may have a role as a vascular neuroprotectant, but the clinical implications are limited by the fact that patients were randomized to placebo instead of aspirin, which is the standard of care.