Low-dose Rivaroxaban plus Antiplatelet Therapy for Symptomatic Intracranial Atherosclerotic Stenosis: A Prospective Cohort Study

Background: The antithrombotic strategies for symptomatic intracranial atherosclerotic stenosis (sICAS) remains challenging. Dual pathway inhibition (DPI) has demonstrated clinical benefit in coronary and peripheral artery disease. Aims: This study aimed to evaluate the efficacy of DPI with low-dose rivaroxaban plus antiplatelet therapy (APT) compared with APT alone on recurrent stroke with sICAS. Methods: This prospective cohort study included patients with sICAS identified from the Ischemic Cerebrovascular Disease Database of the First Affiliated Hospital of Zhengzhou University between January 2019 to August 2023. Low-dose rivaroxaban was prescribed off-label to patients in the DPI group. The outcomes were ischemic stroke, transient ischemic attack (TIA), acute coronary syndrome (ACS), all-cause death and cardio-cerebrovascular death within one year of discharge. Cox regression with inverse probability of treatment weighting (IPTW) was applied to compare outcomes between the DPI and APT groups. The win-ratio method was used to assess the major adverse cardiovascular events (MACE), prioritized in the order of all-cause death, recurrent ischemic stroke or TIA, and ACS. Results: Among the 1217 patients with sICAS, 131 (10.8%) received DPI therapy. The recurrence rate of ischemic stroke was lower in the DPI group compared to the APT group (8/131 6.1% vs. 136/1086 12.5%). DPI significantly reduced the risk of ischemic stroke recurrence (HR=0.46, 95% CI: 0.23-0.94, P=0.034) and the incidence of MACE (HR=0.53, 95% CI: 0.29-0.97, P=0.041) during the 1-year follow-up, consistent with the IPTW-based cohort (HR=0.35, 95% CI: 0.16-0.76, P=0.008; HR=0.43, 95% CI: 0.22-0.83, P=0.012). The win-ratio analysis of MACE favored DPI therapy (win ratio=2.34, 95% CI: 1.41-3.90, P=0.001). Symptomatic intracranial hemorrhage, fatal bleeding, and hospitalization for gastrointestinal bleeding were infrequent in this cohort. Conclusions: DPI therapy may be associated with a lower risk of recurrent stroke compared with antiplatelet therapy alone in patients with sICAS. These findings warrant further investigation through large-scale randomized controlled trials.