Randomized controlled trial of TY-51924, a novel hydrophilic NHE inhibitor, in acute myocardial infarction. Issue 4 (April 2016)

• Record Type: Journal Article
• Authors: Kimura, Kazuo; Nakao, Koichi; Shibata, Yoshisato; Sone, Takahito; Takayama, Tadateru; Fukuzawa, Shigeru; Nakama, Yasuharu; Hirayama, Haruo; Matsumoto, Naoya; Kosuge, Masami; Hiro, Takafumi; Sakuma, Hajime; Ishihara, Masaharu; Asakura, Masanori; Hamada, Chikuma; Kaneko, Akira; Yokoi, Toshiaki; Hirayama, Atsushi
• Is Part Of: Journal of cardiology. Volume 67:Issue 4(2016:Apr.)
• Page Start: 307
• Page End: 313
• Publication Date: 2016-04
• Subjects: Acute myocardial infarction -- Percutaneous coronary intervention -- Reperfusion injury -- Cardioprotection -- NHE inhibitor; Cardiology -- Periodicals; 616.12
• DOI: 10.1016/j.jjcc.2015.07.017
• Languages: English
• ISSNs: 0914-5087

Abstract

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.