CILO-CLOP Trial: Cilostazol Versus Clopidogrel in Acute Moderate and Moderate-to-Severe Ischemic Stroke: A Randomized Controlled Multicenter Trial

INTRODUCTION: All large studies evaluating the role of cilostazol versus other antiplatelet agents in stroke prevention have been conducted in Asia and included patients with minor stroke or transient ischemic attack (TIA). Ours is the first-ever trial to evaluate the safety and efficacy of cilostazol versus clopidogrel in moderate and moderate-to-severe ischemic stroke in North Africa. Accordingly, in this study we assess the role of cilostazol as an alternative to clopidogrel in Egyptian patients with first-ever non-cardioembolic moderate or moderate-to-severe ischemic stroke. METHODS: A total of 870 patients with moderate and moderate-to-severe acute ischemic stroke (AIS) were randomly assigned to administration of loading and maintenance doses of cilostazol or clopidogrel. RESULTS: Of the 870 patients included in our trial, 37 (8.7%) in the cilostazol arm and 59 (13.6%) in the clopidogrel arm experienced a new stroke (HR 0.53; 95% CI, 0.33-0.84; P = 0.007). Twelve participants (2.8%) in the cilostazol group and 25 patients (5.7%) in the clopidogrel group experienced drug-related hemorrhagic complications (HR 0.25; 95% CI, 0.12-0.53; P = 0.001). Patients with hypertension who received cilostazol had significantly lower rates of recurrent hemorrhagic and ischemic stroke. CONCLUSION: Egyptian patients with non-cardioembolic moderate and moderate-to-severe ischemic stroke who received cilostazol within the first 24 h of symptoms had significantly lower rates of hemorrhagic transformation of brain infarction and peripheral hemorrhagic complications than those who received clopidogrel. Patients with hypertension achieved the greatest benefit from cilostazol, as they experienced a significant reduction in recurrent ischemic and hemorrhagic infarction. There were no significant differences between the two groups regarding the modified Rankin scale (mRS) score after 3 months or in the non-hemorrhagic side effects. Our results were derived from a single-blinded study; a more extensive, double-blinded, multinational study is needed for the results to be generalizable worldwide. TRIAL REGISTRATION: Retrospectively registered, ClinicalTrials.gov, NCT06242132, 27-01-2024.