title: Changes in P2Y12 reaction units after switching treatments from prasugrel to clopidogrel in Japanese patients with acute coronary syndrome followed by elective coronary stenting.
abstract: Patients with ischemic heart disease are administered a dual antiplatelet therapy after percutaneous coronary intervention. This consists of aspirin and thienopyridine, which can be switched from prasugrel to clopidogrel. However, the impact of switching is unknown. This study aimed to determine the efficacy and safety of switching from prasugrel to clopidogrel in Japanese patients. One-hundred and thirty-six patients with acute coronary syndrome scheduled to undergo percutaneous coronary intervention and patients with coronary artery disease requiring elective coronary stenting were enrolled. Patients were randomly assigned into the following groups: prasugrel for 6 weeks at loading/maintenance doses of 20/3.75 mg (Continued Group; n = 68) or prasugrel at 20/3.75 mg for 2 weeks followed by clopidogrel at 75 mg for 4 weeks (Switched Group; n = 68). Aspirin (loading dose/maintenance dose 324/81-100 mg/day) was coadministered in both groups. The primary endpoint was the mean P2Y12reaction unit (PRU) at week 6 and the secondary endpoint was the PRU in groups subdivided based on the presence of CYP2C19 gene polymorphisms. At week 6, the PRU was significantly lower in the Continued Group relative to the Switched Group (140.7 and 183.0, respectively; P < 0.001), which was also evident after correction with the baseline values (144.1 vs. 176.6, respectively; P = 0.005). Extensive and poor metabolizers in the Switched Group, based on CYP2C19 gene polymorphisms, had significantly higher PRU values than those in the Continued Group. Thus, switching treatments from prasugrel to clopidogrel significantly increased the PRU in patients receiving antiplatelet therapy subsequent to percutaneous coronary intervention. Clinical Trial Registration UMIN ID, UMIN000015122.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan. takueno@med.kurume-u.ac.jp.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Department of Cardiology, Cardiovascular Center, Miyazaki Medical Association Hospital, Miyazaki, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koiwaya
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Ken-Ichiro
authors.initials: KI
authors.lastname: Sasaki
authors.affiliation: Division of Cardiology, Sugi Hospital, Omuta, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Katsuki
authors.affiliation: Division of Cardiovascular Internal Medicine, Fukuoka City Medical Association Hospital, Fukuoka, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Katsuda
authors.affiliation: Department of Cardiology, Kyushu Medical Center, Fukuoka, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Murasato
authors.affiliation: Division of Cardiovascular Internal Medicine, Tanushimaru Chuo Hospital, Kurume, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Shimamatsu
authors.affiliation: Department of Cardiology, Cardiovascular Center, Shin-Koga Hospital, Kurume, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Umeji
authors.affiliation: Department of Cardiology, Fukuoka Wajiro Hospital, Fukuoka, Japan.
authors.forename: Yoritaka
authors.initials: Y
authors.lastname: Otsuka
authors.affiliation: Department of Cardiology, Cardiovascular Center, Shin-Koga Hospital, Kurume, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kawasaki
authors.affiliation: Department of Cardiology, Cardiovascular Center, Miyazaki Medical Association Hospital, Miyazaki, Japan.
authors.forename: Yoshisato
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukumoto
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000601:surgery*; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011110:Polymorphism, Genetic; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage*; D019919:Prosthesis Implantation; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage*; D011983:Receptors, Purinergic / Q000187:drug effects; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D011983:Receptors, Purinergic; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin
keywords: Clopidogrel; Coronary stent; P2Y12 reaction unit (PRU); Prasugrel; Thienopyridine