title: Optimal cutoff value of P2Y12 reaction units to prevent major adverse cardiovascular events in the acute periprocedural period: post-hoc analysis of the randomized PRASFIT-ACS study.
abstract: BACKGROUND
  Few studies have examined the effects of on-treatment platelet reactivity on the risk of major adverse cardiovascular events (MACE). We aimed to determine the optimal cutoff value of P2Y12 reaction units (PRUs) to prevent MACE occurring within 3days after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS).
  
  
  METHODS
  We performed post-hoc analyses of 1363 patients enrolled in PRASFIT-ACS, which compared the effects of a prasugrel regimen adjusted for Japanese patients (loading dose/maintenance dose: 20mg/3.75mg) with those of clopidogrel (300mg/75mg) on MACE and bleeding events for 24-48weeks after PCI in ACS patients. PRU was serially measured using the VerifyNow® P2Y12 assay and we assessed the relationship between PRU and MACE.
  
  
  RESULTS
  Receiver operating characteristic curve analysis showed that PRU ≤262 at 5-12h after ADP receptor antagonist loading was the optimal cutoff value for preventing MACE at up to 3days after PCI. The incidences of MACE were 5.2% and 10.8% in patients with PRU ≤262 or >262, respectively (odds ratio 0.50, 95% confidence interval 0.25-0.99, p<0.01). Significantly more prasugrel-treated patients had lower on-treatment platelet reactivity (defined as PRU ≤262) compared with clopidogrel-treated patients (79.9% vs. 30.4%, p<0.0001). Similar differences were observed between the prasugrel and clopidogrel groups for patients with normal or reduced-function CYP2C19 alleles.
  
  
  CONCLUSIONS
  The optimal PRU cutoff value for preventing MACE was 262 in Japanese ACS patients. Prasugrel rapidly reduced PRU with a large proportion of patients having low on-treatment platelet reactivity.
authors: Division of Cardiovascular Medicine, Ohashi Medical Center, Toho University, Tokyo, Japan. Electronic address: masato@oha.toho-u.ac.jp.
authors: Masato
authors: M
authors: Nakamura
authors: Division of Cardiology, Teikyo University Hospital, Tokyo, Japan.
authors: Takaaki
authors: T
authors: Isshiki
authors: Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Takeshi
authors: T
authors: Kimura
authors: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, and National Cerebral and Cardiovascular Center, Suita, Japan.
authors: Hisao
authors: H
authors: Ogawa
authors: Fukuoka Sanno Hospital, Fukuoka, and International University of Health and Welfare, Ohtawara, Japan.
authors: Hiroyoshi
authors: H
authors: Yokoi
authors: Superintendent, Nishinomiya Hospital Affairs, Nishinomiya Municipal Central Hospital, Nishinomiya, Japan.
authors: Shinsuke
authors: S
authors: Nanto
authors: Sakakibara Heart Institute, Tokyo, Japan.
authors: Morimasa
authors: M
authors: Takayama
authors: Department of Neurology, Graduate School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
authors: Kazuo
authors: K
authors: Kitagawa
authors: Life Science & Medical Bioscience, Faculty of Science and Engineering, Waseda University, Tokyo, Japan.
authors: Yasuo
authors: Y
authors: Ikeda
authors: Division of Cardiology, Shonan Kamakura General Hospital, Kamakura, Japan.
authors: Shigeru
authors: S
authors: Saito
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000601:surgery; D000368:Aged; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage*; D011300:Preoperative Care / Q000379:methods*; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage; D012372:ROC Curve; D058925:Receptors, Purinergic P2Y12 / Q000097:blood* / Q000187:drug effects; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine
keywords: Acute coronary syndrome; CYP2C19; Clopidogrel; Major adverse cardiovascular event; Platelet reactivity; Prasugrel