ABSTRACT NUMBER: ESOC2026A1057 LP-PLA2 ACTIVITY STRATIFIES BENEFIT FROM IMMEDIATE INTENSIVE STATIN THERAPY IN EMBOLIC STROKE

Abstract Background and aims Whether intensive statin therapy should be initiated immediately after acute ischemic stroke remains uncertain. Embolic stroke and elevated lipoprotein-associated phospholipase A2 (LP-PLA2), reflecting inflammation and plaque instability, may identify patients most likely to benefit from early intensive statin treatment. Methods We conducted a post hoc analysis of the INSPIRES trial, a multicenter, double-blind, placebo-controlled, 2×2 factorial randomized trial including patients with mild ischemic stroke or high-risk transient ischemic attack attributed to atherosclerotic disease. Patients were randomized to immediate or delayed intensive statin therapy. Index strokes were classified as embolic or nonembolic, and baseline LP-PLA2 activity was dichotomized by the median. Interaction analyses assessed whether LP-PLA2 modified the efficacy and safety of immediate intensive statin therapy according to stroke subtype. Outcomes included poor functional outcome (modified Rankin Scale score 2–6), recurrent stroke, and moderate-to-severe bleeding at 90 days. Results Among 5053 patients included, a significant interaction was observed between LP-PLA2 activity and immediate intensive statin therapy for poor functional outcome in embolic stroke (adjusted p for interaction = 0.017), but not in nonembolic stroke. In patients with embolic stroke and high LP-PLA2 activity, immediate intensive statin therapy was associated with a significantly lower risk of poor functional outcome compared with delayed therapy (7.1% vs 13.8%; adjusted RR 0.58, 95% CI 0.40–0.83). No significant differences were observed in recurrent stroke or moderate-to-severe bleeding. Conclusions Immediate intensive statin therapy may provide the greatest functional benefit in patients with embolic stroke and elevated LP-PLA2 activity, supporting a precision approach to early secondary prevention. Conflict of interest Yao Lu, Chenhui Liu, Xuan Wang, Yuesong Pan, Yilong Wang, Ying Gao , Weiqi Chen, Lingling Jiang, Mengyuan Zhou, Yongjun Wang: nothing to disclose