Low-dose ticagrelor combined with aspirin in the prevention of early neurological deterioration of high-risk non-disabling ischemic cerebrovascular events: a PROBE clinical study

BACKGROUND: Early neurological deterioration (END) seriously endangers the clinical prognosis of high-risk non-disabling cerebrovascular events (HR-NICE), and strong antiplatelet therapy is an effective means of preventing the occurrence of END. Studies have confirmed that ticagrelor can avoid the low efficacy of clopidogrel in antiplatelet therapy caused by CYP2C19 gene dysfunction and that its combination with aspirin can improve the clinical prognosis of patients with HR-NICE. However, the overall risk of bleeding events is relatively high. In this protocol, we compared the prevention and safety of END in patients with HR-NICE using aspirin combined with low-dose ticagrelor and aspirin combined with clopidogrel. METHODS AND ANALYSIS: This multicenter, prospective, randomised, open-label, blinded endpoints (PROBE) clinical study intended to enrol 240 patients with HR-NICE who have not undergone reperfusion therapy for block randomization. Ticagrelor combined with aspirin group (120 cases): the patients were given 120 mg of ticagrelor and 100 mg of aspirin orally on the first day of enrollment, and from the next day onwards, ticagrelor 60 mg twice daily orally and aspirin 100 mg daily orally. The clopidogrel combined with aspirin group (120 cases) was administered 300 mg clopidogrel and 100 mg aspirin orally on the first day of enrollment, and starting from the next day, 75 mg clopidogrel and 100 mg aspirin were administered orally. After 21 days, all patients were changed to aspirin 100 mg daily orally. The main efficacy outcome is the early neurological deterioration within 7 days. Safety outcomes include any bleeding events and death. DISCUSSION: This non-inferiority trial will explore whether low-dose ticagrelor combined with aspirin is superior to clopidogrel combined with aspirin for the prevention of END in patients with HR-NICE patients. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of The First Affiliated Hospital of Dalian Medical University (Number Project ID PJ-KS-KY-2023-03(X)). The research results will be published as a journal article. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2300068509. Registered on February 21, 2023. https://www.chictr.org.cn/.