{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T08:24:14Z","timestamp":1751703854457},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The Shenzhen Municipal Science and Technology Foundation","award":["JCYJ20170307100314152","JCYJ20170307100314152"],"award-info":[{"award-number":["JCYJ20170307100314152","JCYJ20170307100314152"]}]},{"name":"The Shenzhen Health Research Fund","award":["SZLY2018011; SZXJ2017029","SZLY2018011; SZXJ2017029","SZLY2018011; SZXJ2017029","SZLY2018011; SZXJ2017029"],"award-info":[{"award-number":["SZLY2018011; SZXJ2017029","SZLY2018011; SZXJ2017029","SZLY2018011; SZXJ2017029","SZLY2018011; SZXJ2017029"]}]},{"name":"The Guangdong Medical Research Fund","award":["A2018008; A2019382","A2018008; A2019382","A2018008; A2019382"],"award-info":[{"award-number":["A2018008; A2019382","A2018008; A2019382","A2018008; A2019382"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cardiovasc Disord"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Trimetazidine (TMZ) pretreatment protects cardiomyocytes during cardiac surgery. TMZ may protect elderly patients with ischaemic heart disease (IHD) undergoing non-cardiac surgery.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This was a randomized, double-blind, placebo-controlled trial (registration #ChiCTR1900025018) of patients with IHD scheduled to undergo non-cardiac surgery at Shenzhen People\u2019s Hospital (Shenzhen, Guangdong Province, China) between June 2014 and September 2015, randomized to 60\u00a0mg TMZ or placebo 12\u00a0h before surgery. The primary endpoint was the occurrence of in-hospital cardiovascular events. The secondary endpoints were myocardial ischaemia on five-lead electrocardiogram (cECG), cardiac troponin I (cTnI) elevation, cardiac death, acute coronary events, heart failure, and arrhythmia requiring treatments.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Compared with the placebo group, the TMZ group showed a lower occurrence of in-hospital cardiovascular events (primary endpoint, 20.0% vs. 37.5%, <jats:italic>P<\/jats:italic>\u2009=\u20090.02), myocardial ischaemia (15.0% vs. 32.5%, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01), cTnI elevation (2.5% vs. 10%, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01), acute coronary events (10.0% vs. 20.0%, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05), heart failure (0% vs. 2.5%, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05), and arrhythmia requiring treatment (17.5% vs. 35.0%, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). There was no acute myocardial infarction during the 30-day postoperative period.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In elderly patients with IHD undergoing non-cardiac surgery, TMZ pretreatment was associated with myocardial protective effects.<\/jats:p>\n                <jats:p><jats:italic>Trial registration<\/jats:italic> The trial was prospectively registered at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.chictr.org.cn\/showproj.aspx?proj=41909\">http:\/\/www.chictr.org.cn\/showproj.aspx?proj=41909<\/jats:ext-link> with registration number [ChiCTR1900025018] (7\/8\/2019).<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12872-021-02287-w","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T14:13:12Z","timestamp":1633097592000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Trimetazidine offers myocardial protection in elderly coronary artery disease patients undergoing non-cardiac surgery: a randomized, double-blind, placebo-controlled trial"],"prefix":"10.1186","volume":"21","author":[{"given":"Zhong-Liang","family":"Dai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Feng","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Li","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,10,1]]},"reference":[{"key":"2287_CR1","first-page":"e596","volume":"140","author":"DK Arnett","year":"2019","unstructured":"Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC\/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;140:e596\u2013646.","journal-title":"Circulation"},{"key":"2287_CR2","doi-asserted-by":"publisher","first-page":"897","DOI":"10.3389\/fphys.2019.00897","volume":"10","author":"R Belli","year":"2019","unstructured":"Belli R, Bonato A, De Angelis L, Mirabilii S, Ricciardi MR, Tafuri A, et al. Metabolic reprogramming promotes myogenesis during aging. Front Physiol. 2019;10:897.","journal-title":"Front Physiol"},{"key":"2287_CR3","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1161\/CIRCULATIONAHA.119.042960","volume":"141","author":"AR Chapman","year":"2020","unstructured":"Chapman AR, Adamson PD, Shah ASV, Anand A, Strachan FE, Ferry AV, et al. High-sensitivity cardiac troponin and the universal definition of myocardial infarction. Circulation. 2020;141:161\u201371.","journal-title":"Circulation"},{"key":"2287_CR4","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.3389\/fimmu.2018.02015","volume":"9","author":"J Chen","year":"2018","unstructured":"Chen J, Wang B, Lai J, Braunstein Z, He M, Ruan G, et al. Trimetazidine attenuates cardiac dysfunction in endotoxemia and sepsis by promoting neutrophil migration. Front Immunol. 2018;9:2015.","journal-title":"Front Immunol"},{"key":"2287_CR5","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1007\/s40265-014-0233-5","volume":"74","author":"P Chrusciel","year":"2014","unstructured":"Chrusciel P, Rysz J, Banach M. Defining the role of trimetazidine in the treatment of cardiovascular disorders: some insights on its role in heart failure and peripheral artery disease. Drugs. 2014;74:971\u201380.","journal-title":"Drugs"},{"key":"2287_CR6","doi-asserted-by":"publisher","first-page":"e1161","DOI":"10.1097\/MD.0000000000001161","volume":"94","author":"LMA Costa","year":"2015","unstructured":"Costa LMA, Rezende PC, Garcia RMR, Uchida AH, Seguro L, Scudeler TL, et al. Role of trimetazidine in ischemic preconditioning in patients with symptomatic coronary artery disease. Medicine. 2015;94:e1161.","journal-title":"Medicine"},{"key":"2287_CR7","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.ihj.2017.04.001","volume":"69","author":"JJ Dalal","year":"2017","unstructured":"Dalal JJ, Mishra S. Modulation of myocardial energetics: an important category of agents in the multimodal treatment of coronary artery disease and heart failure. Indian Heart J. 2017;69:393\u2013401.","journal-title":"Indian Heart J"},{"key":"2287_CR8","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1139\/cjpp-2016-0424","volume":"95","author":"A Danikiewicz","year":"2017","unstructured":"Danikiewicz A, Szkodzi\u0144ski J, Hudzik B, Korzonek-Szlacheta I, G\u0105sior M, Zubelewicz-Szkodzi\u0144ska B. Effects of trimetazidine on interleukin-2 and interleukin-8 concentrations in patients with coronary artery disease. Can J Physiol Pharmacol. 2017;95:759\u201362.","journal-title":"Can J Physiol Pharmacol"},{"key":"2287_CR9","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.accpm.2018.02.021","volume":"37","author":"JL Fellahi","year":"2018","unstructured":"Fellahi JL, Godier A, Benchetrit D, Berthier F, Besch G, Bochaton T, et al. Perioperative management of patients with coronary artery disease undergoing non-cardiac surgery: summary from the French Society of Anaesthesia and Intensive Care Medicine 2017 convention. Anaesthesia Crit Care Pain Med. 2018;37:367\u201374.","journal-title":"Anaesthesia Crit Care Pain Med"},{"key":"2287_CR10","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1111\/anae.14447","volume":"73","author":"MT Ferguson","year":"2018","unstructured":"Ferguson MT, Hofman MS, Ismail H, Melville A, Yap KSK, Hicks RJ, et al. A pilot study of cardiopulmonary exercise testing and cardiac stress positron emission tomography before major non-cardiac surgery. Anaesthesia. 2018;73:1524\u201330.","journal-title":"Anaesthesia"},{"key":"2287_CR11","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1007\/s12325-018-0674-4","volume":"35","author":"M Glezer","year":"2018","unstructured":"Glezer M. The Effectiveness of trimetazidine treatment in patients with stable angina pectoris of various durations: results from the CHOICE-2 study. Adv Ther. 2018;35:1103\u201313.","journal-title":"Adv Ther"},{"key":"2287_CR12","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1159\/000369246","volume":"130","author":"YC Liu","year":"2015","unstructured":"Liu YC, Li L, Su Q, Liu T, Tang ZL. Trimetazidine pretreatment inhibits myocardial apoptosis and improves cardiac function in a Swine model of coronary microembolization. Cardiology. 2015;130:130\u20136.","journal-title":"Cardiology"},{"key":"2287_CR13","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.ijcard.2019.05.063","volume":"293","author":"M Marzilli","year":"2019","unstructured":"Marzilli M, Vinereanu D, Lopaschuk G, Chen Y, Dalal JJ, Danchin N, et al. Trimetazidine in cardiovascular medicine. Int J Cardiol. 2019;293:39\u201344.","journal-title":"Int J Cardiol"},{"key":"2287_CR14","doi-asserted-by":"publisher","first-page":"649","DOI":"10.2217\/cer-2017-0011","volume":"6","author":"Z Meiszterics","year":"2017","unstructured":"Meiszterics Z, K\u00f3nyi A, Hild G, S\u00e1rszegi Z, Gaszner B. Effectiveness and safety of anti-ischemic trimetazidine in patients with stable angina pectoris and type 2 diabetes. J Compar Effect Res. 2017;6:649\u201357.","journal-title":"J Compar Effect Res"},{"issue":"Suppl 1","key":"2287_CR15","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1111\/anae.14138","volume":"73","author":"D Sellers","year":"2018","unstructured":"Sellers D, Srinivas C, Djaiani G. Cardiovascular complications after non-cardiac surgery. Anaesthesia. 2018;73(Suppl 1):34\u201342.","journal-title":"Anaesthesia"},{"key":"2287_CR16","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1177\/0267659117696140","volume":"32","author":"JJ Sistino","year":"2017","unstructured":"Sistino JJ, Fitzgerald DC. Epidemiology of cardiovascular disease in the United States: implications for the perfusion profession. A 2017 update. Perfusion. 2017;32:501\u20136.","journal-title":"Perfusion"},{"key":"2287_CR17","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1159\/000478067","volume":"42","author":"Q Su","year":"2017","unstructured":"Su Q, Li L, Zhao J, Sun Y, Yang H. Effects of Trimetazidine on PDCD4\/NF-\u03baB\/TNF-\u03b1 pathway in coronary microembolization. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol. 2017;42:753\u201360.","journal-title":"Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol"},{"key":"2287_CR18","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1093\/ehjcvp\/pvx029","volume":"4","author":"JM Tarkin","year":"2018","unstructured":"Tarkin JM, Kaski JC. Trimetazidine: is there a role beyond angina? Eur Heart J Cardiovasc Pharmacother. 2018;4:67\u20138.","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"key":"2287_CR19","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.ijcard.2019.07.093","volume":"300","author":"U Thadani","year":"2020","unstructured":"Thadani U. Trimetazidine for stable and unstable ischemic heart diseases and for heart failure: is its routine use justified from available data? Int J Cardiol. 2020;300:45\u20136.","journal-title":"Int J Cardiol"},{"key":"2287_CR20","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1177\/0003319714530040","volume":"66","author":"K Tsioufis","year":"2015","unstructured":"Tsioufis K, Andrikopoulos G, Manolis A. Trimetazidine and cardioprotection: facts and perspectives. Angiology. 2015;66:204\u201310.","journal-title":"Angiology"},{"key":"2287_CR21","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1161\/CIRCULATIONAHA.108.778019","volume":"118","author":"H Tuunanen","year":"2008","unstructured":"Tuunanen H, Engblom E, Naum A, N\u00e5gren K, Scheinin M, Hesse B, et al. Trimetazidine, a metabolic modulator, has cardiac and extracardiac benefits in idiopathic dilated cardiomyopathy. Circulation. 2008;118:1250\u20138.","journal-title":"Circulation"},{"key":"2287_CR22","first-page":"2018","volume":"104","author":"JA Valle","year":"2018","unstructured":"Valle JA, Graham L, Thiruvoipati T, Grunwald G, Armstrong EJ, Maddox TM, et al. Facility-level association of preoperative stress testing and postoperative adverse cardiac events. Heart (British Cardiac Society). 2018;104:2018\u201325.","journal-title":"Heart (British Cardiac Society)"},{"key":"2287_CR23","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1161\/CIR.0000000000000580","volume":"138","author":"AS Volgman","year":"2018","unstructured":"Volgman AS, Palaniappan LS, Aggarwal NT, Gupta M, Khandelwal A, Krishnan AV, et al. Atherosclerotic Cardiovascular Disease in South Asians in the United States: Epidemiology, Risk Factors, and Treatments: A Scientific Statement From the American Heart Association. Circulation. 2018;138:e1\u201334.","journal-title":"Circulation"},{"key":"2287_CR24","doi-asserted-by":"publisher","first-page":"343","DOI":"10.4070\/kcj.2016.46.3.343","volume":"46","author":"M Yaman","year":"2016","unstructured":"Yaman M, Arslan U, G\u00fcmr\u00fck\u00e7\u00fco\u011flu HA, \u015eahin M, \u015eim\u015fek H, Akda\u011f S. Effects of Trimetazidine on T Wave Alternans in Stable Coronary Artery Disease. Korean circulation journal. 2016;46:343\u20139.","journal-title":"Korean circulation journal"},{"key":"2287_CR25","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3389\/fphar.2019.00175","volume":"10","author":"H Zhang","year":"2019","unstructured":"Zhang H, Liu M, Zhang Y, Li X. Trimetazidine attenuates exhaustive exercise-induced myocardial injury in rats via regulation of the Nrf2\/NF-\u03baB signaling pathway. Front Pharmacol. 2019;10:175.","journal-title":"Front Pharmacol"},{"key":"2287_CR26","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/j.jacc.2011.11.027","volume":"59","author":"L Zhang","year":"2012","unstructured":"Zhang L, Lu Y, Jiang H, Zhang L, Sun A, Zou Y, et al. Additional use of trimetazidine in patients with chronic heart failure: a meta-analysis. J Am Coll Cardiol. 2012;59:913\u201322.","journal-title":"J Am Coll Cardiol"},{"key":"2287_CR27","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1159\/000375289","volume":"131","author":"N Zhang","year":"2015","unstructured":"Zhang N, Lei J, Liu Q, Huang W, Xiao H, Lei H. The effectiveness of preoperative trimetazidine on myocardial preservation in coronary artery bypass graft patients: a systematic review and meta-analysis. Cardiology. 2015;131:86\u201396.","journal-title":"Cardiology"},{"key":"2287_CR28","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1097\/FJC.0000000000000487","volume":"69","author":"Y Zhong","year":"2017","unstructured":"Zhong Y, Zhong P, He S, Zhang Y, Tang L, Ling Y, et al. Trimetazidine Protects Cardiomyocytes Against Hypoxia\/Reoxygenation Injury by Promoting AMP-activated Protein Kinase-dependent Autophagic Flux. J Cardiovasc Pharmacol. 2017;69:389\u201397.","journal-title":"J Cardiovasc Pharmacol"},{"key":"2287_CR29","doi-asserted-by":"publisher","DOI":"10.4244\/EIJ-D-21-00181","author":"F Gragnano","year":"2021","unstructured":"Gragnano F, Spirito A, Corpataux N, Vaisnora L, Galea R, Gargiulo G, Siontis GCM, Praz F, Lanz J, Billinger M, Hunziker L, Stortecky S, Pilgrim T, B\u00e4r S, Ueki Y, Capodanno D, Urban P, Pocock SJ, Mehran R, Heg D, Windecker S, R\u00e4ber L, Valgimigli M. Impact of clinical presentation on bleeding risk after percutaneous coronary intervention and implications for the ARC-HBR definition. EuroIntervention. 2021. https:\/\/doi.org\/10.4244\/EIJ-D-21-00181.","journal-title":"EuroIntervention"},{"issue":"3","key":"2287_CR30","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1161\/CIRCULATIONAHA.119.040167","volume":"140","author":"P Urban","year":"2019","unstructured":"Urban P, Mehran R, Colleran R, Angiolillo DJ, Byrne RA, Capodanno D, Cuisset T, Cutlip D, Eerdmans P, Eikelboom J, Farb A, Gibson CM, Gregson J, Haude M, James SK, Kim HS, Kimura T, Konishi A, Laschinger J, Leon MB, Magee PFA, Mitsutake Y, Mylotte D, Pocock S, Price MJ, Rao SV, Spitzer E, Stockbridge N, Valgimigli M, Varenne O, Windhoevel U, Yeh RW, Krucoff MW, Morice MC. Defining high bleeding risk in patients undergoing percutaneous coronary intervention. Circulation. 2019;140(3):240\u201361.","journal-title":"Circulation"}],"container-title":["BMC Cardiovascular Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12872-021-02287-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12872-021-02287-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12872-021-02287-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T14:13:20Z","timestamp":1633097600000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccardiovascdisord.biomedcentral.com\/articles\/10.1186\/s12872-021-02287-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,1]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2287"],"URL":"https:\/\/doi.org\/10.1186\/s12872-021-02287-w","relation":{},"ISSN":["1471-2261"],"issn-type":[{"value":"1471-2261","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,1]]},"assertion":[{"value":"21 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Shenzhen People's Hospital Ethics Committee, Guangdong, China (Chairperson Prof MJ. Tang, Ethics Committee Number LL-KT-2014028). All subjects were properly informed of the risks and procedures of the research before enrolment. All participants provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"473"}}