Low-dose ticagrelor combined with aspirin for preventing early neurological deterioration in patients with high-risk non-disabling ischemic cerebrovascular events: a multicenter, prospective, randomized, open-label, clinical trial

BACKGROUND: Early neurological deterioration (END) is associated with a poor prognosis in patients with high‑risk non‑disabling ischemic cerebrovascular events (HR‑NICE). Clopidogrel-based dual antiplatelet therapy is substantially limited by the CYP2C19 gene polymorphism. This study aimed to investigate whether low‑dose ticagrelor (60 mg twice daily) plus aspirin dual antiplatelet therapy was superior to clopidogrel plus aspirin for preventing END within 7 days in HR-NICE patients, without increasing the bleeding risk. METHODS: This was a multicenter, prospective, randomized, open-label, blinded-endpoint clinical trial conducted in China. Patients with HR‑NICE within 24 h of onset were enrolled. They were randomly assigned to receive low-dose ticagrelor (60 mg twice daily) plus aspirin (TA group) or clopidogrel plus aspirin (LA group) in a 1:1 ratio. The primary outcome was END within 7 days, defined as a ≥ 2-point National Institutes of Health Stroke Scale (NIHSS) score increase or NIHSS motor score ≥ 1-point compared with baseline. Secondary outcomes included an excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 90 days and major ischemic vascular events within 90 days. Safety outcomes included any bleeding events. Intention‑to‑treat analysis was performed in this trial. RESULTS: A total of 334 patients were randomized to the TA group (n=167) or the LA group (n=167). The incidence of END within 7 days was 10.8% (18/167) in the TA group and 22.2% (37/167) in the LA group (relative risk [RR], 0.55; 95% CI, 0.33-0.92; p=0.023). At 90 day follow-up, 92.8% and 80.8% of patients had an excellent functional outcome in the TA and LA groups, respectively (RR, 1.13; 95% CI, 1.05-1.23; p=0.002). For ischemic vascular events within 90 days, there were no significant differences between groups (6.6% versus 10.8%; RR, 0.54; 95% CI, 0.26-1.09; p=0.085). Any bleeding events occurred in 10 patients (6.0%) in the TA group and 7 patients (4.2%) in the LA group (RR, 1.32; 95% CI, 0.51-3.43; p=0.563), all mild. Adverse events (12.6% vs 10.2%, p=0.467) and serious adverse events (0.6% vs 1.8%, p=0.339) were also similar between groups. CONCLUSION: Among patients with HR‑NICE within 24 h of onset, low‑dose ticagrelor plus aspirin significantly decreased the incidence of END within 7 days and improved neurological functional outcomes at 90 days compared with clopidogrel plus aspirin, without increasing the risk of bleeding. This regimen may provide a safe and effective alternative antiplatelet strategy for END prevention in institutions lacking rapid genotyping facilities. TRIAL REGISTRATION: http://www.chictr.org.cn . Identifier: ChiCTR2300068509. Date of registration: February 21, 2023.