title: Randomized controlled trial of TY-51924, a novel hydrophilic NHE inhibitor, in acute myocardial infarction.
abstract: BACKGROUND
  In patients with ST-elevation acute myocardial infarction (STEMI), reperfusion therapy limits infarct size, but can directly evoke myocardial reperfusion injury. Activation of the Na(+)/H(+) exchanger (NHE) plays an important role in reperfusion injury. TY-51924, a novel NHE inhibitor, significantly reduced infarct size in animal studies and was well tolerated in early-phase clinical trials. This study aim was to evaluate the efficacy and safety of TY-51924 in patients with STEMI.
  
  
  METHODS
  In this multicenter, randomized, double-blind, placebo-controlled Phase II trial, 105 patients with first anterior STEMI undergoing primary percutaneous coronary intervention (pPCI) were randomly assigned to receive an intravenous infusion of either TY-51924 or placebo. Primary endpoints were myocardial salvage index (MSI) as determined by single photon emission computed tomography (SPECT) 3-5 days after pPCI and safety up to 7 days.
  
  
  RESULTS
  Baseline characteristics were similar in the two groups. MSI 3-5 days after pPCI (0.200 vs. 0.290, p=0.56), 3 months after pPCI (0.470 vs. 0.500, p=0.76), and the incidences of side effects did not differ between the two groups as a whole. However, on post hoc analysis of 52 patients with a large area at risk (AAR) (≥38%) and no antegrade coronary flow, MSI by SPECT at 3 months after pPCI was significantly higher in TY-51924 group (0.450 vs. 0.320, p=0.03). TY-51924 did not adversely influence hemodynamics.
  
  
  CONCLUSIONS
  TY-51924 did not improve MSI or increase side effects as a whole. However, TY-51924 is potentially cardioprotective in the presence of a large AAR and no antegrade coronary flow.
authors.affiliation: Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan. Electronic address: c-kimura@urahp.yokohama-cu.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakao
authors.affiliation: Cardiology, Miyazaki Medical Association Hospital, Miyazaki, Japan.
authors.forename: Yoshisato
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: Department of Cardiology, Ogaki Municipal Hospital, Ogaki, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Sone
authors.affiliation: Department of Cardiology, Nihon University Itabashi Hospital, Tokyo, Japan.
authors.forename: Tadateru
authors.initials: T
authors.lastname: Takayama
authors.affiliation: Division of Cardiology, Funabashi Municipal Medical Center Heart and Vascular Institute, Funabashi, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Fukuzawa
authors.affiliation: Department of Cardiology, Hiroshima City Hospital, Hiroshima, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nakama
authors.affiliation: Department of Cardiology, Nagoya Daini Red Cross Hospital, Nagoya, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Hirayama
authors.affiliation: Department of Cardiology, Nihon University Hospital, Tokyo, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Cardiology, Yokohama Ekisaikai Hospital, Yokohama, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Kosuge
authors.affiliation: Division of Advanced Cardiovascular Image Analysis, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Hiro
authors.affiliation: Department of Radiology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Sakuma
authors.affiliation: Division of Coronary Artery Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ishihara
authors.affiliation: Department of Clinical Research, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Asakura
authors.affiliation: Faculty of Engineering, Tokyo University of Science, Tokyo, Japan.
authors.forename: Chikuma
authors.initials: C
authors.lastname: Hamada
authors.affiliation: Research & Development Department, TOA EIYO Ltd., Saitama, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kaneko
authors.affiliation: Research & Development Department, TOA EIYO Ltd., Saitama, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Yokoi
authors.affiliation: Department of Medicine, Division of Cardiology, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirayama
mesh_terms: D000208:Acute Disease; D000368:Aged; D000818:Animals; D004311:Double-Blind Method; D005260:Female; D006146:Guanidines / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000209:etiology; D009206:Myocardium / Q000473:pathology; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013463:Sulfuric Acid Esters / Q000627:therapeutic use*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C000592017:3-guanidinocarbonyl-2-methyl-6,7,8,9-tetrahydro-5H-cyclohepta(b)pyridine-9-ylmethyl sulfuric acid; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013463:Sulfuric Acid Esters
keywords: Acute myocardial infarction; Cardioprotection; NHE inhibitor; Percutaneous coronary intervention; Reperfusion injury