title: Risk of bleeding and repeated bleeding events in prasugrel-treated patients: a review of data from the Japanese PRASFIT studies.
abstract: Prasugrel is a third-generation thienopyridine that achieves potent platelet inhibition with less pharmacological variability than other thienopyridines. However, clinical experience suggests that prasugrel may be associated with a higher risk of de novo and recurrent bleeding events compared with clopidogrel in Japanese patients undergoing percutaneous coronary intervention (PCI). In this review, we evaluate the risk of bleeding in Japanese patients treated with prasugrel at the doses (loading/maintenance doses: 20/3.75 mg) adjusted for Japanese patients, evaluate the risk factors for bleeding in Japanese patients, and examine whether patients with a bleeding event are at increased risk of recurrent bleeding. This review covers published data and new analyses of the PRASFIT (PRASugrel compared with clopidogrel For Japanese patIenTs) trials of patients undergoing PCI for acute coronary syndrome or elective reasons. The bleeding risk with prasugrel was similar to that observed with the standard dose of clopidogrel (300/75 mg), including when bleeding events were re-classified using the Bleeding Academic Research Consortium criteria. The pharmacodynamics of prasugrel was not associated with the risk of bleeding events. The main risk factors for bleeding events were female sex, low body weight, advanced age, and presence of diabetes mellitus. Use of a radial puncture site was associated with a lower risk of bleeding during PCI than a femoral puncture site. Finally, the frequency and severity of recurrent bleeding events during continued treatment were similar between prasugrel and clopidogrel. In summary, this review provides important insights into the risk and types of bleeding events in prasugrel-treated patients.Trial registration numbers: JapicCTI-101339 and JapicCTI-111550.
authors.affiliation: Clinical Research Support Center, Mie University Hospital, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan. nisikawa@clin.medic.mie-u.ac.jp.
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Nishikawa
authors.affiliation: Division of Cardiology, Ageo Central General Hospital, Saitama, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Isshiki
authors.affiliation: Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Cardiovascular Medicine Center, Fukuoka Sanno Hospital, Fukuoka, Japan.|International University of Health and Welfare, Tochigi, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Yokoi
authors.affiliation: Saiseikai Tondabayashi Hospital, Osaka, Japan.|Division of Cardiology, Department of Medicine, Faculty of Medicine, Kinki University, Osaka, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Miyazaki
authors.affiliation: 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: R&D Division, Biostatistics & Data Management Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Division of Cardiology, Shonan Kamakura General Hospital, Kamakura, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saito
mesh_terms: D054058:Acute Coronary Syndrome / Q000601:surgery*; D023903:Coronary Restenosis / Q000517:prevention & control; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D019106:Postoperative Hemorrhage / Q000139:chemically induced / Q000453:epidemiology*; D000068799:Prasugrel Hydrochloride / Q000009:adverse effects* / Q000627:therapeutic use; D012008:Recurrence; D012307:Risk Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D000068799:Prasugrel Hydrochloride
keywords: Bleeding; Clopidogrel; Pharmacology; Prasugrel