P2Y₁₂ Reaction Units With Prasugrel in Acute Large Artery Atherosclerosis and Transient Ischemic Attack: An Open-Label Randomized Controlled Study, ACUTE-PRAS

BACKGROUND: The antiplatelet effect of prasugrel for acute ischemic stroke or transient ischemic attack (TIA) remains unclear. This study compared platelet reactivity between prasugrel and clopidogrel, considering cytochrome P450 family 2 subfamily C member 19 (CYP2C19) gene polymorphisms (extensive metabolizers [EM], intermediate metabolizers [IM], and poor metabolizers [PM]), in patients with acute large artery atherosclerosis (LAA) or high-risk TIA. METHODS AND RESULTS: In this multicenter open-label randomized controlled study, patients with acute LAA or high-risk TIA received prasugrel or clopidogrel with aspirin. The primary endpoint was platelet reaction units (PRU) 5 days after the start of drug administration, stratified according to CYP2C19 polymorphism. In all, 176 patients participated (88 in each group). Compared with the clopidogrel group, PRU on Day 5 in the prasugrel group were significantly lower in the overall population (adjusted mean 136.0 vs. 169.9; estimated difference -33.9; 95% confidence interval [CI] -49.0, -18.8), EM group (118.5 vs. 144.8; estimated difference -26.2; 95% CI -48.0, -4.4), and IM group (140.3 vs. 173.1; estimated difference -32.8; 95% CI -56.6, -9.0), and tended to be lower in the PM group (164.7 vs. 196.2; estimated difference -31.6; 95% CI -68.3, 5.1). The prevalence of new infarct lesions was comparable between the prasugrel and clopidogrel groups, as was the incidence of adverse events (30.7% vs. 26.1%, respectively) and bleeding events up to Day 5 of administration. CONCLUSIONS: In patients with acute LAA or high-risk TIA, prasugrel resulted in stable inhibition of platelet aggregation 5 days after starting drug administration compared with clopidogrel, regardless of CYP2C19 polymorphisms.