Toward Optimal Antiplatelet Therapy in Acute Ischemic Stroke: What Can We Learn from a <i>Post Hoc</i> Subgroup Analysis of the ACUTE-PRAS Study?

Antiplatelet therapy for early secondary prevention after ischemic stroke remains a cornerstone of stroke medicine, particularly in patients with large artery atherosclerosis and high-risk transient ischemic attack (TIA), in whom the risk of early recurrence is substantial.Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel has become standard in select patients with minor stroke or TIA 1,2) .However, variability in the clopidogrel response driven by genetic, metabolic, and clinical factors continues to challenge a "one-size-fits-all" treatment approach.Additionally, prasugrel, an alternative to clopidogrel, is less dependent on CYP2C19 genetic polymorphisms for its activity 3) , thus making it a potentially more reliable treatment option for patients with acute ischemic events.In this context, a post hoc, hypothesisgenerating, exploratory analysis of the ACUTE-PRAS study by Fujimoto et al. provides timely and clinically relevant insights into the heterogeneity of platelet inhibition by P2Y12 inhibitors in the acute cerebrovascular ischemic setting 4) .The primary ACUTE-PRAS study demonstrated that prasugrel achieved a greater reduction in platelet reaction units (PRU) on day 5 compared with clopidogrel, independent of CYP2C19 genetic polymorphisms 5) .The present post hoc analysis extends these findings by examining whether this pharmacodynamic advantage is preserved across clinically relevant patient subgroups, including an advanced age, hypertension, chronic kidney disease (CKD), diabetes mellitus (DM), dyslipidemia, a low body mass index (BMI), prior ischemic stroke, early treatment initiation, and differing stroke severity.This approach addresses a key unmet need in stroke practice: identifying patient profiles in whom more potent and reliable platelet inhibition may be particularly advantageous.