Randomized controlled trial of TY-51924, a novel hydrophilic NHE inhibitor, in acute myocardial infarction

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• 作者：Kazuo Kimura ; MD ; PhD ; FJCC^a ; ^{c-kimura@urahp.yokohama-cu.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Koichi Nakao ; MD ; PhD ; FJCC^b ; Yoshisato Shibata ; MD^c ; Takahito Sone ; MD ; PhD ; FJCC^d ; Tadateru Takayama ; MD ; PhD^e ; Shigeru Fukuzawa ; MD ; PhD ; FJCC^f ; Yasuharu Nakama ; MD^g ; Haruo Hirayama ; MD ; PhD ; FJCC^h ; Naoya Matsumoto ; MD ; PhD ; FJCCⁱ ; Masami Kosuge ; MD ; PhD^j ; Takafumi Hiro ; MD ; PhD ; FJCC^k ; Hajime Sakuma ; MD ; PhD^l ; Masaharu Ishihara ; MD ; PhD ; FJCC^m ; Masanori Asakura ; MD ; PhDⁿ ; Chikuma Hamada ; PhD^o ; Akira Kaneko ; MS^p ; Toshiaki Yokoi ; MS^p ; Atsushi Hirayama ; MD ; PhD ; FJCC^q ; for the AMITY study group
• 关键词：Acute myocardial infarction ; Percutaneous coronary intervention ; Reperfusion injury ; Cardioprotection ; NHE inhibitor
• 刊名：Journal of Cardiology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：67
• 期：4
• 页码：307-313
• 全文大小：435 K

文摘

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.