Randomized Controlled Trial of Cilostazol Addition for In-Stent Restenosis After Carotid Artery Stenting

BACKGROUND: Restenosis after carotid artery stenting (CAS) is associated with the risk of developing ischemic stroke. We aimed to evaluate the inhibitory effect of cilostazol addition on in-stent restenosis (ISR) in patients treated with CAS. METHODS: In a randomized, open-label, blind-end point trial, patients with symptomatic and asymptomatic carotid artery stenosis and scheduled for CAS were randomly assigned to adding cilostazol (50 or 100 mg, twice per day) on other antiplatelets from 3 days before CAS or not adding cilostazol. Concomitant use of other antiplatelets was unrestricted. ISR was diagnosed by a peak systolic velocity of at least 1.75 m/s on duplex ultrasonography. The primary outcome was incidence of ISR within 2 years after CAS. Secondary outcomes included occurrences of cardiovascular events or any death and hemorrhagic events. RESULTS: Participants were recruited from December 2010 to September 2015. Although the sample size was initially set to be 900 (450 in each group), 631 patients (mean age 69.9 years, 558 men, 325 in the cilostazol, and 306 in the noncilostazol group) were included in the primary analysis. Within 2 years’ follow-up, ISR occurred in 31 of 325 patients (cumulative incidence 10.8%) in the cilostazol group and 46 of 306 patients (19.6%) in the noncilostazol group (hazard ratio, 0.64 [95% CI, 0.41–1.0]; P =0.056). In the exploratory analysis, incidence of ISR beyond 30 days after CAS was lower in the cilostazol group than in the noncilostazol group (10.3% versus 19.3%; P =0.040). Incidences of cardiovascular events or any death and hemorrhagic events were similar between the groups (6.2% versus 6.7% and 2.3% versus 1.4%, respectively). CONCLUSIONS: The addition of cilostazol to other antiplatelet agents could contribute to the reduction of ISR in the chronic stage of patients who underwent CAS, the authenticity of which depends on further studies with sufficient statistical power. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01261234.