{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:33:50Z","timestamp":1790883230680,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T00:00:00Z","timestamp":1694995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Cardiology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Sodium\u2013glucose cotransporter 2 (SGLT2) inhibitors are emerging antidiabetic agents with various potential cardiovascular benefits. The EMPT\u2010ANGINA trial examined the effect of empagliflozin on the angina burden in those with concurrent type 2 diabetes mellitus (T2DM) and refractory angina (RA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>In this 8\u2010week, double\u2010blind, randomized, placebo\u2010controlled trial, 75 patients with T2DM and RA were randomly assigned to one of two groups: empagliflozin (<jats:italic>n<\/jats:italic>\u2009=\u200937) and placebo (<jats:italic>n<\/jats:italic>\u2009=\u200938). The primary outcome was an improvement in angina, which was assessed by the Seattle Angina Questionnaire (SAQ). The secondary outcomes of this study included alterations in the SAQ domains and exercise test components.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mean age of individuals in the empagliflozin and placebo groups was 67.46\u2009\u00b1\u20099.4 and 65.47\u2009\u00b1\u20097.0 years, respectively (<jats:italic>p<\/jats:italic>\u2009=\u2009.304). Patients who received empagliflozin showed a significant improvement in both the primary endpoint, which was the SAQ Summary Score (192.73\u2009\u00b1\u200920.70 vs. 224\u2009\u00b1\u200925.36, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001) and the secondary endpoints. Exercise test components, including treadmill exercise duration, time till angina, 1\u2009mm ST\u2010segment depression onset, and heart rate (HR) recovery, were all significantly improved in the empagliflozin group. This positive impact was reached with no clinically significant changes in resting and exertion HR or blood pressure. There were no significant side effects in the empagliflozin group (<jats:italic>p<\/jats:italic>\u2009=\u2009.125).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Empagliflozin can be safely added as a metabolic modulator agent to existing antianginal medications in individuals with concurrent T2DM and RA to reduce angina symptoms and enhance exercise capacity with minimal side effects.<\/jats:p><\/jats:sec>","DOI":"10.1002\/clc.24158","type":"journal-article","created":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T12:49:54Z","timestamp":1695041394000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Antianginal effects of empagliflozin in patients with type 2 diabetes\u00a0and refractory angina; a randomized, double\u2010blind placebo\u2010controlled trial (EMPT\u2010ANGINA Trial)"],"prefix":"10.1002","volume":"47","author":[{"given":"Mohammad Hadi","family":"Mansouri","sequence":"first","affiliation":[{"name":"Hypertension Research Center, Cardiovascular Research Institute Isfahan University of Medical Sciences Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6407-0241","authenticated-orcid":false,"given":"Pejman","family":"Mansouri","sequence":"additional","affiliation":[{"name":"Tehran Heart Center Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoumeh","family":"Sadeghi","sequence":"additional","affiliation":[{"name":"Cardiac Rehabilitation Research Center, Cardiovascular Research Institute Isfahan University of Medical Sciences Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8253-203X","authenticated-orcid":false,"given":"Seyedeh Melika","family":"Hashemi","sequence":"additional","affiliation":[{"name":"Tehran Heart Center Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Khosravi","sequence":"additional","affiliation":[{"name":"Hypertension Research Center, Cardiovascular Research Institute Isfahan University of Medical Sciences Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohaddeseh","family":"Behjati","sequence":"additional","affiliation":[{"name":"Cardiac Rehabilitation Research Center, Cardiovascular Research Institute Isfahan University of Medical Sciences Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javad","family":"Shahabi","sequence":"additional","affiliation":[{"name":"Heart Failure Research Center, Cardiovascular Research Institute Isfahan University of Medical Sciences Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asieh","family":"Mansouri","sequence":"additional","affiliation":[{"name":"Hypertension Research Center, Cardiovascular Research Institute Isfahan University of Medical Sciences Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reihaneh","family":"Zavar","sequence":"additional","affiliation":[{"name":"Isfahan Cardiovascular Research Center, Cardiovascular Research Institute Isfahan University of Medical Sciences Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afshin","family":"Amirpour","sequence":"additional","affiliation":[{"name":"Cardiac Rehabilitation Research Center, Cardiovascular Research Institute Isfahan University of Medical Sciences Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid","family":"Sanei","sequence":"additional","affiliation":[{"name":"Isfahan Cardiovascular Research Center, Cardiovascular Research Institute Isfahan University of Medical Sciences Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nizal","family":"Sarrafzadegan","sequence":"additional","affiliation":[{"name":"Isfahan Cardiovascular Research Center, Cardiovascular Research Institute Isfahan University of Medical Sciences Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.310961"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.022194"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3909\/ricm0742"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.02.011"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/14746514030030010301"},{"key":"e_1_2_10_7_1","first-page":"155","article-title":"Optimal treatment of chronic angina in patients with type 2 diabetes mellitus","volume":"5","author":"Kaur H","year":"2014","journal-title":"Res Rep Clin Cardiol"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht190"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2013.200"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.15420\/ecr.2016:26:1"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(00)00732-4"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(03)00062-1"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ehj.2004.02.018"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2018.10.002"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4509-7"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv728"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.032038"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.034222"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1811744"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32590-X"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.038868"},{"issue":"2","key":"e_1_2_10_22_1","first-page":"86","article-title":"Neutrophil to lymphocyte ratio is significantly reduced after sodium glucose cotransporter\u20102 inhibitor treatment in patients with type 2 diabetes mellitus","volume":"18","author":"Kurtkulagi O","year":"2022","journal-title":"Int J Endocrinol"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11845-021-02761-6"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.09.020"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.2337\/dci18-0033"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-0542"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1520-765X(01)90147-6"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(94)00397-9"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2018.04.012"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.5144\/0256-4947.2006.1"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.3.309"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1586\/erc.11.149"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2008.11.004"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2017.131"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.014908"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3180"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-015-3547-2"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.004007"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-019-4859-4"},{"issue":"3","key":"e_1_2_10_40_1","first-page":"191","article-title":"Tofogliflozin, a highly selective inhibitor of SGLT2 blocks proinflammatory and proapoptotic effects of glucose overload on proximal tubular cells partly by suppressing oxidative stress generation","volume":"48","author":"Ishibashi Y","year":"2016","journal-title":"Horm Metab Res"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0165703"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/jch.13174"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.2217\/cer-2017-0011"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161208786071317"},{"issue":"1","key":"e_1_2_10_45_1","first-page":"135","article-title":"An imbalance between glycolysis and glucose oxidation is a possible explanation for the detrimental effects of high levels of fatty acids during aerobic reperfusion of ischemic hearts","volume":"264","author":"Lopaschuk GD","year":"1993","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.86.5.580"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.33594\/000000178"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-019-0820-6"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-018-4644-9"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"issue":"2","key":"e_1_2_10_51_1","article-title":"Cardiovascular and renal benefits of SGLT2 inhibitors: a narrative review","volume":"17","author":"Rabizadeh S","year":"2019","journal-title":"Int J Endocrinol Metab"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-018-4670-7"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-017-0621-8"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1080\/00325481.2019.1581971"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(97)00996-X"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.038881"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.2337\/db18-1154-P"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00421"}],"container-title":["Clinical Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/clc.24158","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T09:17:18Z","timestamp":1706865438000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/clc.24158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,18]]},"references-count":57,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/clc.24158"],"URL":"https:\/\/doi.org\/10.1002\/clc.24158","archive":["Portico"],"relation":{},"ISSN":["0160-9289","1932-8737"],"issn-type":[{"value":"0160-9289","type":"print"},{"value":"1932-8737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,18]]},"assertion":[{"value":"2023-06-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e24158"}}