{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:29:36Z","timestamp":1792682976294,"version":"4.5.0"},"reference-count":26,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Objective<\/jats:title><jats:p>To explore the effect of adding trimetazidine to other anti-anginal drugs on the functional capacity of ischemic heart disease (IHD) patients not suitable for revascularization when compared to first-line antianginal drugs alone.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p>MEDLINE and EMBASE databases were searched for English-language peer-reviewed randomized controlled trials (RCTs) comparing trimetazidine with first-line antianginal drugs alone or with placebo in IHD patients not suitable for revascularization and were included in this review. Quality of studies were assessed using the Cochrane collaboration \u201crisk of bias\u201d tool.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>Six RCTs, three were crossover studies. A total of 312 participants were included in this review. Overall quality of studies was moderate. Two studies found improvement in the 6-minute walking test (6-MWT) [standardized mean differences (SMD) 1.75; 95% CI 1.35 to 2.14; p &lt;0.001], and two trials found improvement in the Canadian cardiovascular society (CCS) grading of angina class (SMD -1.37; 95% CI -1.89 to -0.84) in the trimetazidine group. Three of the better-quality trials found no increase in total exercise duration (TED) (SMD 0.34; 95% CI -0.10 to 0.78; p &lt; 0.13). Significant heterogeneity was identified among trials describing outcomes for the New York Heart Association (NYHA) functional classification and left ventricular ejection fraction (LVEF %).<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusion<\/jats:title><jats:p>Trimetazidine improve walking time and angina severity in IHD patients not suitable for revascularization. Due to the inconsistency of available evidence, RCTs targeting IHD patients with \u201cno option\u201d to undergo coronary revascularization is required to clarify this review question.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0263932","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T18:27:25Z","timestamp":1644604045000},"page":"e0263932","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effect of trimetazidine on the functional capacity of ischemic heart disease patients not suitable for revascularization: Meta-analysis of randomized controlled trials"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5154-6183","authenticated-orcid":true,"given":"Alyaa","family":"Ajabnoor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amnah","family":"Mukhtar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,11]]},"reference":[{"key":"pone.0263932.ref001","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/nrcardio.2013.200","article-title":"Treatment of refractory angina in patients not suitable for revascularization","volume":"11","author":"TD Henry","year":"2014","journal-title":"Nat Rev Cardiol"},{"issue":"23","key":"pone.0263932.ref002","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1136\/heartjnl-2015-308564","article-title":"Alternative interventions for refractory angina","volume":"103","author":"PA Sainsbury","year":"2017","journal-title":"Heart"},{"key":"pone.0263932.ref003","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1053\/euhj.2001.2706","article-title":"The problem of chronic refractory angina: Report from the ESC Joint Study Group on the treatment of refractory angina","volume":"23","author":"C Mannheimer","year":"2002","journal-title":"Eur Heart J"},{"key":"pone.0263932.ref004","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2165\/00129784-200303001-00002","article-title":"The pursuit of optimum outcomes in stable angina","volume":"3","author":"U. 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Society Joint Guidelines","volume":"28","author":"M McGillion","year":"2012","journal-title":"Can J Cardiol"},{"issue":"4","key":"pone.0263932.ref011","doi-asserted-by":"crossref","first-page":"264","DOI":"10.7326\/0003-4819-151-4-200908180-00135","article-title":"Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement","volume":"151","author":"D Moher","year":"2009","journal-title":"Ann Intern Med"},{"issue":"4","key":"pone.0263932.ref012","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0120519","article-title":"The method quality of cross-over studies involved in Cochrane Systematic Reviews","volume":"10","author":"H Ding","year":"2015","journal-title":"PLoS One"},{"key":"pone.0263932.ref013","article-title":"Chapter 23: Including variants on randomized trials","author":"J Higgins","year":"2011","journal-title":"Cochrane handbook for systematic reviews of interventions Version 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patients with angina pectoris: Results of three studies","volume":"12","author":"H Szwed","year":"2001","journal-title":"Coron Artery Dis"},{"issue":"10","key":"pone.0263932.ref023","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1111\/j.1742-1241.2003.tb10632.x","article-title":"Trimetazidine in geriatric patients with stable angina pectoris: The tiger study","volume":"57","author":"F K\u00f6lbel","year":"2003","journal-title":"Int J Clin Pract"},{"key":"pone.0263932.ref024","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1097\/00045391-200501000-00006","article-title":"Trimetazidine in angina combination therapy\u2014The TACT study: Trimetazidine versus conventional treatment in patients with stable angina pectoris in a randomized, placebo-controlled, multicenter study","volume":"12","author":"EI Chazov","year":"2005","journal-title":"Am J Ther"},{"key":"pone.0263932.ref025","first-page":"1","article-title":"2019 ESC guidelines for the diagnosis and management of 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