{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:38:19Z","timestamp":1792798699843,"version":"4.5.0"},"reference-count":50,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"unspecified","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CVON","award":["2020B008RECONNEXT"],"award-info":[{"award-number":["2020B008RECONNEXT"]}]},{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["dr. E.Dekker Senior Clinical Scientist Grant 2020T"],"award-info":[{"award-number":["dr. E.Dekker Senior Clinical Scientist Grant 2020T"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["dr. E.Dekker Senior Post-Doc Grant 2018T059"],"award-info":[{"award-number":["dr. E.Dekker Senior Post-Doc Grant 2018T059"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Netherlands Organization for Scientific Research","award":["NWO-VIDI: 917.18.338"],"award-info":[{"award-number":["NWO-VIDI: 917.18.338"]}],"id":[{"id":"https:\/\/ror.org\/04jsz6e67","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Netherlands CardioVasculair Research Initiative","award":["2017-10:Dolphin-Genesis"],"award-info":[{"award-number":["2017-10:Dolphin-Genesis"]}]},{"name":"Netherlands CardioVasculair Research Initiative","award":["CVON 2018-29: PHAEDRA-IMPACT"],"award-info":[{"award-number":["CVON 2018-29: PHAEDRA-IMPACT"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Open Heart"],"accepted":{"date-parts":[[2024,3,21]]},"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite maximal treatment, heart failure (HF) remains a major clinical challenge. Besides neurohormonal overactivation, myocardial energy homoeostasis is also impaired in HF. Trimetazidine has the potential to restore myocardial energy status by inhibiting fatty acid oxidation, concomitantly enhancing glucose oxidation. Trimetazidine is an interesting adjunct treatment, for it is safe, easy to use and comes at a low cost.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We conducted a systematic review to evaluate all available clinical evidence on trimetazidine in HF. We searched Medline\/PubMed, Embase, Cochrane CENTRAL and ClinicalTrials.gov to identify relevant studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Out of 213 records, we included 28 studies in the meta-analysis (containing 2552 unique patients), which almost exclusively randomised patients with HF with reduced ejection fraction (HFrEF). The studies were relatively small (median study size: N=58) and of short duration (mean follow-up: 6 months), with the majority (68%) being open label.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Trimetazidine in HFrEF was found to significantly reduce cardiovascular mortality (OR 0.33, 95% CI 0.21 to 0.53) and HF hospitalisations (OR 0.42, 95% CI 0.29 to 0.60). In addition, trimetazidine improved (New York Heart Association) functional class (mean difference: \u22120.44 (95% CI \u22120.49 to \u22120.39), 6\u2009min walk distance (mean difference: +109\u2009m (95% CI 105 to 114\u2009m) and quality of life (standardised mean difference: +0.52 (95% CI 0.32 to 0.71). A similar pattern of effects was observed for both ischaemic and non-ischaemic cardiomyopathy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Current evidence supports the potential role of trimetazidine in HFrEF, but this is based on multiple smaller trials of varying quality in study design. We recommend a large pragmatic randomised clinical trial to establish the definitive role of trimetazidine in the management of HFrEF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/openhrt-2023-002579","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T12:55:16Z","timestamp":1715172916000},"page":"e002579","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["Effects of trimetazidine on heart failure with reduced ejection fraction and associated clinical outcomes: a systematic review and meta-analysis"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2042-9469","authenticated-orcid":false,"given":"Soufiane","family":"Nassiri","sequence":"first","affiliation":[{"name":"Cardiology, Amsterdam University Medical Centres, Amsterdam, Netherlands"},{"name":"Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arno A","family":"Van de Bovenkamp","sequence":"additional","affiliation":[{"name":"Cardiology, Amsterdam University Medical Centres, Amsterdam, Netherlands"},{"name":"Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Remmelzwaal","sequence":"additional","affiliation":[{"name":"Epidemiology & Biostatistics, Amsterdam University Medical Centres, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olimpia","family":"Sorea","sequence":"additional","affiliation":[{"name":"Cardiology, Amsterdam University Medical Centres, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"de Man","sequence":"additional","affiliation":[{"name":"Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands"},{"name":"Pulmonary Medicine, Amsterdam University Medical Centres, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Louis","family":"Handoko","sequence":"additional","affiliation":[{"name":"Cardiology, Amsterdam University Medical Centres, Amsterdam, Netherlands"},{"name":"Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"key":"2025081709572294000_11.1.e002579.1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab368"},{"key":"2025081709572294000_11.1.e002579.2","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.jacc.2021.10.043","article-title":"Lifetime risk of heart failure among participants in the Framingham study","volume":"79","author":"Vasan","year":"2022","journal-title":"J Am Coll Cardiol"},{"key":"2025081709572294000_11.1.e002579.3","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(92)90167-L"},{"key":"2025081709572294000_11.1.e002579.4","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2016.203"},{"key":"2025081709572294000_11.1.e002579.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra063052"},{"key":"2025081709572294000_11.1.e002579.6","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehi816"},{"key":"2025081709572294000_11.1.e002579.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.05.012"},{"key":"2025081709572294000_11.1.e002579.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.11.060"},{"key":"2025081709572294000_11.1.e002579.9","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/ddr.21654","article-title":"Effect of age and renal impairment on the pharmacokinetics and safety of Trimetazidine: an open-label multiple-dose study","volume":"81","author":"Nenchev","year":"2020","journal-title":"Drug Dev Res"},{"key":"2025081709572294000_11.1.e002579.10","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2010.208751"},{"key":"2025081709572294000_11.1.e002579.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.11.027"},{"key":"2025081709572294000_11.1.e002579.12","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0094660","article-title":"Is treatment with Trimetazidine beneficial in patients with chronic heart failure","volume":"9","author":"Zhou","year":"2014","journal-title":"PLoS ONE"},{"key":"2025081709572294000_11.1.e002579.13","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1159\/000375288","article-title":"The effect of Trimetazidine added to pharmacological treatment on all-cause mortality in patients with systolic heart failure","volume":"131","author":"Grajek","year":"2015","journal-title":"Cardiology"},{"key":"2025081709572294000_11.1.e002579.14","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1007\/s00059-015-4392-2","article-title":"Trimetazidine improves exercise tolerance in patients with ischemic heart disease: a meta-analysis","volume":"41","author":"Zhao","year":"2016","journal-title":"Herz"},{"key":"2025081709572294000_11.1.e002579.15","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.31083\/j.rcm2204149","article-title":"The efficacy of Trimetazidine in non-ischemic heart failure patients: a meta-analysis of randomized controlled trials","volume":"22","author":"Zhao","year":"2021","journal-title":"Rev Cardiovasc Med"},{"key":"2025081709572294000_11.1.e002579.16","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"2025081709572294000_11.1.e002579.17","article-title":"Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for systematic reviews of interventions","volume":"10","author":"Cumpston","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"key":"2025081709572294000_11.1.e002579.18","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.l4898","article-title":"Rob 2: A revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"2025081709572294000_11.1.e002579.19","doi-asserted-by":"publisher","DOI":"10.1097\/00006199-200207000-00001"},{"key":"2025081709572294000_11.1.e002579.20","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1017\/S2045796016000809","article-title":"Pre-post effect sizes should be avoided in meta-analyses","volume":"26","author":"Cuijpers","year":"2017","journal-title":"Epidemiol Psychiatr Sci"},{"key":"2025081709572294000_11.1.e002579.21","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1001\/jamacardio.2018.4847","article-title":"Effect of Trimetazidine dihydrochloride therapy on exercise capacity in patients with Nonobstructive hypertrophic cardiomyopathy: a randomized clinical trial","volume":"4","author":"Coats","year":"2019","journal-title":"JAMA Cardiol"},{"key":"2025081709572294000_11.1.e002579.22","doi-asserted-by":"crossref","first-page":"2998","DOI":"10.1002\/ehf2.14418","article-title":"Trimetazidine in heart failure with preserved ejection fraction: a randomised controlled cross-over trial","volume":"10","author":"van de Bovenkamp","year":"2023","journal-title":"ESC Heart Fail"},{"key":"2025081709572294000_11.1.e002579.23","doi-asserted-by":"crossref","first-page":"65","DOI":"10.18087\/cardio.2021.11.n1801","article-title":"Efficacy of Trimetazidine - an inhibitor of free fatty acids oxidation in the treatment of patients with stable angina Pectoris and heart failure","volume":"61","author":"Bubnova","year":"2021","journal-title":"Kardiologiia"},{"key":"2025081709572294000_11.1.e002579.24","first-page":"15","article-title":"Potentialities of cytoprotection in the treatment of chronic heart failure in patients with coronary heart disease","volume":"82","author":"Fedorova","year":"2004","journal-title":"Klin Med (Mosk)"},{"key":"2025081709572294000_11.1.e002579.25","first-page":"35","article-title":"Clinico-economical aspects of application of Trimetazidine MB in patients with chronic heart failure and cardiac rhythm disturbances","volume":"51","author":"Morozova","year":"2011","journal-title":"Kardiologiia"},{"key":"2025081709572294000_11.1.e002579.26","first-page":"62","article-title":"A clinical experience of Taurine and Trimetazidine use in premenopausal women with chronic heart failure","volume":"50","author":"Sedova","year":"2010","journal-title":"Kardiologiia"},{"key":"2025081709572294000_11.1.e002579.27","first-page":"81","article-title":"Management of angina attacks in heart failure due to Noncoronary heart disease: Trimetazidine usage","volume":"127","author":"Sitnikova","year":"2015","journal-title":"Russian J Cardiol"},{"key":"2025081709572294000_11.1.e002579.28","first-page":"51","article-title":"Comparative trial of efficacy of Trimethasidine MB and 3-(2,2,2-Trimethylhydrasine) propionate Dihydrate in chronic heart failure","volume":"79","author":"Vasiuk","year":"2007","journal-title":"Ter Arch"},{"key":"2025081709572294000_11.1.e002579.29","first-page":"4549","article-title":"Efficacy and safety of metoprolol plus Trimetazidine in treating coronary heart failure","volume":"28","author":"Zhang","year":"2017","journal-title":"Biomed Res"},{"key":"2025081709572294000_11.1.e002579.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ehj.2004.06.034"},{"key":"2025081709572294000_11.1.e002579.31","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1007\/s12471-020-01407-z","article-title":"Trimetazidine as a performance-enhancING drug in heart failure with preserved ejection fraction (Doping-Hfpef): rationale and design of a placebo-controlled cross-over intervention study","volume":"28","author":"van de Bovenkamp","year":"2020","journal-title":"Neth Heart J"},{"key":"2025081709572294000_11.1.e002579.32","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1161\/CIRCULATIONAHA.122.062166","article-title":"Retained metabolic flexibility of the failing human heart","volume":"148","author":"Watson","year":"2023","journal-title":"Circulation"},{"key":"2025081709572294000_11.1.e002579.33","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.061846"},{"key":"2025081709572294000_11.1.e002579.34","doi-asserted-by":"crossref","first-page":"627","DOI":"10.5603\/CJ.a2020.0165","article-title":"Effects of Trimetazidine in patients with severe chronic heart failure with reduced left ventricular ejection fraction: a prospective, randomized, open-label, cross-over study","volume":"29","author":"Bohdan","year":"2022","journal-title":"Cardiol J"},{"key":"2025081709572294000_11.1.e002579.35","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/BF00051293","article-title":"Cardioprotective effect of Trimetazidine in severe ischemic cardiomyopathy","volume":"4 Suppl 4","author":"Bricaud","year":"1990","journal-title":"Cardiovasc Drugs Ther"},{"key":"2025081709572294000_11.1.e002579.36","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.eurheartj.a059685"},{"key":"2025081709572294000_11.1.e002579.37","doi-asserted-by":"publisher","DOI":"10.1177\/1074248409356431"},{"key":"2025081709572294000_11.1.e002579.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.03.060"},{"key":"2025081709572294000_11.1.e002579.39","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2011.226332"},{"key":"2025081709572294000_11.1.e002579.40","doi-asserted-by":"publisher","DOI":"10.1007\/s00380-008-1118-x"},{"key":"2025081709572294000_11.1.e002579.41","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.ihj.2016.04.023","article-title":"Metabolic manipulation in dilated cardiomyopathy: assessing the role of Trimetazidine","volume":"68","author":"Jatain","year":"2016","journal-title":"Indian Heart J"},{"key":"2025081709572294000_11.1.e002579.42","doi-asserted-by":"publisher","DOI":"10.2165\/00129784-200505040-00006"},{"key":"2025081709572294000_11.1.e002579.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ihj.2016.03.021"},{"key":"2025081709572294000_11.1.e002579.44","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e31814fa9cb"},{"key":"2025081709572294000_11.1.e002579.45","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.ahj.2007.06.033","article-title":"Beneficial effects of Trimetazidine treatment on exercise tolerance and B-type natriuretic peptide and troponin T plasma levels in patients with stable ischemic cardiomyopathy","volume":"154","author":"Di Napoli","year":"2007","journal-title":"Am Heart J"},{"key":"2025081709572294000_11.1.e002579.46","first-page":"155","article-title":"Efficacy of valsartan combined with Trimetazidine in the treatment of chronic heart failure and effects on cardiac function","volume":"13","author":"Qin","year":"2020","journal-title":"Int J Clin Exp Med"},{"key":"2025081709572294000_11.1.e002579.47","doi-asserted-by":"publisher","DOI":"10.2143\/AC.62.5.2023413"},{"key":"2025081709572294000_11.1.e002579.48","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.778019"},{"key":"2025081709572294000_11.1.e002579.49","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2020.00459","article-title":"Shenmai injection improves energy metabolism in patients with heart failure: a randomized controlled trial","volume":"11","author":"Wang","year":"2020","journal-title":"Front Pharmacol"},{"key":"2025081709572294000_11.1.e002579.50","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.cardfail.2014.01.004","article-title":"Effects of Trimetazidine in nonischemic heart failure: a randomized study","volume":"20","author":"Winter","year":"2014","journal-title":"J Card Fail"}],"container-title":["Open Heart"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/openhrt-2023-002579","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,17]],"date-time":"2025-08-17T16:57:34Z","timestamp":1755449854000},"score":1,"resource":{"primary":{"URL":"https:\/\/openheart.bmj.com\/lookup\/doi\/10.1136\/openhrt-2023-002579"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,5,8]]},"published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1136\/openhrt-2023-002579"],"URL":"https:\/\/doi.org\/10.1136\/openhrt-2023-002579","relation":{},"ISSN":["2053-3624"],"issn-type":[{"value":"2053-3624","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5]]}}}