P2Y12 Inhibitor Response By Patient Background Factors: An Exploratory Post Hoc Subgroup Analysis of the ACUTE-PRAS Study

Abstract

Aim: To explore whether the antiplatelet effects of prasugrel and clopidogrel vary according to patient background factors in the ACUTE-PRAS study.

Methods: This was a post hoc, hypothesis-generating, exploratory analysis of the multicenter, open-label, randomized controlled ACUTE-PRAS study, in which 176 patients with acute atherothrombotic stroke or high-risk TIA received prasugrel or clopidogrel within 48 h of symptom onset. High platelet reactivity (HPR; platelet reaction units [PRU] ＞208) and absolute PRU were assessed on Day 5 in subgroups stratified by ABCD-GENE score, age, body mass index (BMI), chronic kidney disease (CKD), diabetes mellitus (DM), hypertension, dyslipidemia, time from stroke onset to treatment, National Institutes of Health Stroke Scale (NIHSS) score, and prior ischemic stroke.

Results: Patients with prasugrel had numerically lower rates of HPR than those with clopidogrel in the high-risk stratum of ABCD-GENE score ≥ 10 (OR 2.73, p = 0.076), and favorable trends in prasugrel were also observed for CKD (8.06, p = 0.012), age ＞75 years (5.02, p = 0.025), BMI ＜25 kg/m² (4.61, p = 0.012), dyslipidemia (4.73, p = 0.009), DM (3.86, p = 0.038), treatment initiation ≤ 24 h (3.31, p = 0.010), and NIHSS ≤ 3 (2.77, p = 0.036) or ≥ 4 (9.00, p = 0.025). Prasugrel also reduced PRU numerically more than clopidogrel across most subgroups, except in patients with BMI ≥ 25 kg/m², treatment initiation ＞24 hours, or prior ischemic stroke, where only numerical differences were observed.

Conclusions: Prasugrel provided favorable early platelet inhibition, particularly in subgroups characterized by advanced age, CKD, low BMI, metabolic comorbidities, or very early treatment start.

Keywords: Clopidogrel; Ischemic event; Platelet reaction units; Platelet reactivity; Prasugrel.