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

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, 0.84 [95% CI, 0.65–1.09]). The P value was 0.45 for the treatment × Lp-PLA2 activity interaction effect on stroke recurrence. The risk of bleeding associated with ticagrelor–aspirin did not differ across Lp-PLA2 activity levels. CONCLUSIONS: In patients with minor stroke or transient ischemic attack carrying CYP2C19 loss-of-function alleles, elevated Lp-PLA2 activity did not significantly modify the efficacy or safety of dual antiplatelet therapy. Further research is needed to clarify the potential role of Lp-PLA2 in guiding individualized treatment decisions. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04078737.