title: No association between on-treatment platelet reactivity and bleeding events following percutaneous coronary intervention and antiplatelet therapy: A post hoc analysis.
abstract: BACKGROUND
  Few studies have examined the relationship between the pharmacodynamics of antiplatelet drugs and the risk of clinically significant bleeding following percutaneous coronary intervention (PCI) for treating acute coronary syndrome (ACS). We examined the associations between the pharmacodynamics of prasugrel and clopidogrel and the incidence of bleeding events in the acute and chronic phases after PCI.
  
  
  METHODS
  We performed a post hoc analysis of the PRASFIT-ACS (PRASugrel compared with clopidogrel For Japanese patIenTs with ACS undergoing PCI) study of patients in whom platelet reactivity was determined as P2Y12 reaction units (PRU; VerifyNow® P2Y12 assay) or vasodilator-stimulated phosphoprotein-phosphorylation reactivity index (VASP-PRI). Japanese patients were randomized to prasugrel (loading/maintenance dose: 20/3.75 mg) or clopidogrel (300/75 mg), both in combination with aspirin, for 24-48 weeks. The bleeding outcome was a composite of major, minor, and clinically relevant bleeding.
  
  
  RESULTS
  Overall, 66/685 (9.6%) and 65/678 (9.6%) of prasugrel- and clopidogrel-treated patients, respectively, experienced major, minor, or clinically relevant bleeding. PRU and VASP-PRI at 5-12h or in steady state conditions (at 4 weeks) were not associated with the risk of bleeding in the acute (to day 3) or chronic (from day 4 to 14 days after treatment discontinuation) phases of treatment, respectively. Less than 9% of patients with low on-treatment platelet reactivity (defined as PRU<85 or VASP-PRI<16) experienced bleeding events.
  
  
  CONCLUSIONS
  No direct association of the pharmacodynamics of prasugrel and clopidogrel with the risk of bleeding was observed in this cohort of Japanese ACS patients following PCI.
authors.affiliation: Clinical Research Support Center, Mie University Hospital, Mie, Japan. Electronic address: nisikawa@clin.medic.mie-u.ac.jp.
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Nishikawa
authors.affiliation: Ageo Central General Hospital, Ageo, Saitama, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Isshiki
authors.affiliation: Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto and National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Fukuoka Sanno Hospital, Fukuoka, Japan; International University of Health and Welfare, Ohtawara, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Yokoi
authors.affiliation: Division of Cardiology, Department of Medicine, Faculty of Medicine, Kinki University, Osaka, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Miyazaki
authors.affiliation: Life Science & Medical Bioscience, Faculty of Science and Engineering, Waseda University, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Division of Cardiovascular Medicine, Ohashi Medical Center, Toho University, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Clinical Data & Biostatistics Department, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takita
authors.affiliation: Division of Cardiology, Shonan Kamakura General Hospital, Kamakura, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saito
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D006470:Hemorrhage / Q000188:drug therapy*; D006801:Humans; D008297:Male; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*
chemical_list: D010975:Platelet Aggregation Inhibitors
keywords: Acute coronary syndrome; Clopidogrel; Hemorrhage; Platelet function tests; Prasugrel