By Matthew E. Fink, MD

Louis and Gertrude Feil Professor and Chair, Department of Neurology, Associate Dean for Clinical Affairs, New York Presbyterian/Weill Cornell Medical College

Dr. Fink reports no financial relationships relevant to this field of study.

SOURCE: McHutchison C, Blair GW, Appleton JP, et al. Cilostazol for secondary prevention of stroke and cognitive decline: Systematic review and meta-analysis. Stroke 2020; July 10. doi: 10.1161/STROKEAHA.120.029454. [Online ahead of print].

Cilostazol is a phosphodiesterase 3 inhibitor widely used in Asia for secondary stroke prevention but approved for use in North America only for symptomatic peripheral vascular disease. In animal studies, it has been demonstrated to have weak antiplatelet effects, but it stabilizes the endothelium and appears to aid myelin repair. It has been theorized that cilostazol might be beneficial in preventing the progression of small vessel disease in the brain and, therefore, may have a secondary effect in preventing vascular dementia.

The investigators undertook a systematic review and meta-analysis of randomized controlled trials of cilostazol to prevent stroke, cognitive decline, or small vessel disease progression in studies published from Jan. 1, 2019, until July 16, 2019, and they pooled the data for analysis. They calculated odds ratios (ORs) and 95% confidence intervals (CIs) for recurrent ischemic stroke, hemorrhagic stroke, death, and adverse symptoms.

They identified 20 randomized controlled trials, which included 10,505 patients, 18 studies in ischemic stroke and two in cognitive impairment. In a pooled analysis, researchers found that cilostazol decreased recurrent ischemic stroke (OR, 0.68; P < 0.0001), hemorrhagic stroke (OR, 0.43; P = 0.0001), deaths (OR, 0.64; P < 0.0009), and systemic bleeding (OR, 0.73; P = 0.04), but they noted an increased incidence of headache and palpitations when compared to placebo, aspirin, or clopidogrel. Cilostazol appeared to have greater benefit when given long term vs. short term (greater than six months) and did not increase hemorrhages. The data were insufficient to assess its effects on cognition, imaging, or functional outcomes.

The majority of these studies were performed in Asia-Pacific countries, and more trials in Western countries should be initiated to assess the effects of cilostazol treatment on cognitive decline and functional outcomes, as well as on the progression of small vessel disease in the brain. The studies from Asia suggest that it is a promising treatment, but it has not been studied sufficiently in clinical trials.