Objective:

We evaluated whether baseline and post-loading (Day 3) platelet activation profiles predict long-term
recurrence of acute ischemic stroke and other vascular events.

Background:

Patients with ischemic stroke face a substantial 3-4% annual risk of recurrent vascular events despite guideline-directed secondary prevention.  Conventional clinical scores (e.g., Essen, SPI-II) summarize demographics and co-morbidities but do not capture patient-specific thrombotic biology. We evaluated whether baseline and post-loading (Day 3) platelet activation profiles predict long-term
recurrence.

Design/Methods:

This was a single-centre prospective cohort study at the National University Hospital,
Singapore, enrolling adults with non-cardioembolic ischemic stroke. Platelet activation markers were
quantified by flow cytometry in isolated platelets at presentation, and Day 3 after guideline-directed antiplatelet loading. Age-matched healthy individuals served as controls. The prespecified primary outcome was a composite of ischemic stroke/TIA, myocardial infarction, peripheral arterial occlusion, vascular death over 5 years, adjudicated quarterly. Multivariable Cox models (adjusted for age, stroke severity, and antiplatelet regimen) assessed associations between markers and outcome. Multiple-
marker testing was controlled by false-discovery rate.

Results:

381 patients (mean age 58.9 years, 74% male) were enrolled with median follow-up 47 months; 100 events occurred (26.2%). Relative to 50 healthy controls, 8/10 platelet activation markers were elevated at baseline. By Day 3, antiplatelet therapy reduced several platelet activation markers (CLEC-2, COX-1, GPVI, PAC-1, SDF-1, and CD154), whereas CXCR7, CD62P, COX-2, and P2Y12 remained persistently high. In adjusted analyses, Day 3 platelet CXCR7 independently predicted recurrence (HR 2.34; 95% CI 1.02–5.35; p = 0.045), while baseline markers were not predictive.

Conclusions:

A residual CXCR7-linked platelet signature persists despite standard antiplatelet therapy. Day 3 platelet CXCR7 independently predicts long-term vascular recurrence and merits prospective validation, alongside mechanistic studies to determine whether
CXCR7-pathway modulation can reduce residual thrombotic risk.