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. 2025 May 16.
doi: 10.1253/circj.CJ-24-0949. Online ahead of print.

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

Shigeru Fujimoto  1 , Yasuyuki Iguchi  2 , Hiroshi Yamagami  3   4 , Masatoshi Koga  5 , Ryo Itabashi  6 , Yusuke Yakushiji  7 , Kazuma Kowata  8 , Naoto Kimura  9   10 , Yuka Terasawa  11 , Takahiro Shimizu  12 , Yuichi Miyazaki  13 , Koichi Oki  14 , Osamu Masuo  15 , Hideki Matsuoka  16 , Shuji Arakawa  17 , Toshihiro Ueda  18 , Ryota Tanaka  1 , Wataru Hashimoto  19 , Satoru Abe  20 , Go Kato  20 , Taketoshi Furugori  20 , Kazumi Kimura  21 ; ACUTE-PRAS Investigators
Affiliations

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

Shigeru Fujimoto et al. Circ J. .

Abstract

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.

Keywords: Atherothrombotic stroke; Clopidogrel; Cytochrome P450 family 2 subfamily C member 19 (CYP2C19); Prasugrel; Transient ischemic attack.

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