Lp-PLA2 Activity and Genotype-Guided Dual Antiplatelet Therapy in Minor Stroke or Transient Ischemic Attack

作者：Jinxi Lin, Hongyu Zhou, Yubo Wang, Aoming Jin, Shangzhi Li, L J Zhang, Xia Meng, XueWei Peng YingGang Xie, Jing Jing, Yong Jiang, Yilong Wang, X H Zhao, H. Li, Zixiao Li, Yongjun Wang, for the CHANCE-2 Investigators · 发表于：Stroke · 年份：2026 · DOI：10.1161/strokeaha.125.052954 · 研究领域：Protease and Inhibitor Mechanisms、Blood Coagulation and Thrombosis Mechanisms、Lysosomal Storage Disorders Research

BACKGROUND: Lp-PLA2 (lipoprotein-associated phospholipase A2) is a sensitive biomarker of vascular inflammation and atherosclerosis. This study evaluated the influence of Lp-PLA2 activity on the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin among patients with minor stroke or transient ischemic attack carrying CYP2C19 loss-of-function alleles. METHODS: The CHANCE-2 trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events-II) randomized 6412 patients with minor stroke or transient ischemic attack carrying CYP2C19 loss-of-function alleles to receive ticagrelor-aspirin or clopidogrel-aspirin. This subgroup study included patients with available baseline Lp-PLA2 activity measurements, stratified by the median value of 188.4 nmol/min per milliliter. The primary efficacy and safety outcomes were stroke recurrence and severe or moderate bleeding events within 90 days. Associations between treatment and outcomes were assessed using multivariable Cox proportional hazards models, adjusting for a history of hyperlipidemia. RESULTS: A total of 5919 patients were included (mean age, 64.4 years; 33.9% female). Among patients with low Lp-PLA2 activity, ticagrelor-aspirin reduced the 90-day risk of recurrent stroke compared with clopidogrel-aspirin (5.4% versus 7.4%; adjusted hazard ratio, 0.72 [95% CI, 0.54–0.97]). In patients with high Lp-PLA2 activity, no significant difference was observed (6.9% versus 8.2%; adjusted hazard ratio, 0.8...