{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:16:29Z","timestamp":1790662589893,"version":"4.1.0"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000291","name":"Kidney Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000291","id-type":"DOI","asserted-by":"publisher"}]},{"name":"British Heart Foundation Centre of Research Excellence","award":["RE\/18\/6\/34217"],"award-info":[{"award-number":["RE\/18\/6\/34217"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>To investigate the effect of high-dose iron vs. low-dose intravenous (IV) iron on myocardial infarction (MI) in patients on maintenance haemodialysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>This was a pre-specified analysis of secondary endpoints of the Proactive IV Iron Therapy in Hemodialysis Patients trial (PIVOTAL) randomized, controlled clinical trial. Adults who had started haemodialysis within the previous year, who had a ferritin concentration &amp;lt;400 \u03bcg per litre and a transferrin saturation &amp;lt;30% were randomized to high-dose or low-dose IV iron. The main outcome measure for this analysis was fatal or non-fatal MI. Over a median of 2.1 years of follow-up, 8.4% experienced a MI. Rates of type 1 MIs (3.2\/100 patient-years) were 2.5 times higher than type 2 MIs (1.3\/100 patient-years). Non-ST-elevation MIs (3.3\/100 patient-years) were 6 times more common than ST-elevation MIs (0.5\/100 patient-years). Mortality was high after non-fatal MI (1- and 2-year mortality of 40% and 60%, respectively). In time-to-first event analyses, proactive high-dose IV iron reduced the composite endpoint of non-fatal and fatal MI [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.52\u20130.93, P = 0.01] and non-fatal MI (HR 0.69, 95% CI 0.51\u20130.93; P = 0.01) when compared with reactive low-dose IV iron. There was less effect of high-dose IV iron on recurrent MI events than on the time-to-first event analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In total, 8.4% of patients on maintenance haemodialysis had an MI over 2 years. High-dose compared to low-dose IV iron reduced MI in patients receiving haemodialysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>EudraCT Registration Number<\/jats:title><jats:p>2013-002267-25.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cvr\/cvab317","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T20:45:30Z","timestamp":1633034730000},"page":"213-220","source":"Crossref","is-referenced-by-count":16,"title":["High-dose intravenous iron reduces myocardial infarction in patients on haemodialysis"],"prefix":"10.1093","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6333-9496","authenticated-orcid":false,"given":"Mark C","family":"Petrie","sequence":"first","affiliation":[{"name":"BHF Cardiovascular Research Centre, University of Glasgow , 126 University Place, Glasgow G12 8TA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4306-5317","authenticated-orcid":false,"given":"Pardeep S","family":"Jhund","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Research Centre, University of Glasgow , 126 University Place, Glasgow G12 8TA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5625-2344","authenticated-orcid":false,"given":"Eugene","family":"Connolly","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Research Centre, University of Glasgow , 126 University Place, Glasgow G12 8TA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3387-2123","authenticated-orcid":false,"given":"Patrick B","family":"Mark","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Research Centre, University of Glasgow , 126 University Place, Glasgow G12 8TA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3501-3592","authenticated-orcid":false,"given":"Michael R","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Changi General Hospital , Singapore , Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8425-2592","authenticated-orcid":false,"given":"Michele","family":"Robertson","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics, University of Glasgow , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3331-7314","authenticated-orcid":false,"given":"Stefan D","family":"Anker","sequence":"additional","affiliation":[{"name":"Charite, Universitatsmedizin Berlin , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2748-3095","authenticated-orcid":false,"given":"Sunil","family":"Bhandari","sequence":"additional","affiliation":[{"name":"Hull and East Yorkshire Hospitals NHS Trust and Hull York, Medical School , Hull , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8862-6056","authenticated-orcid":false,"given":"Kenneth","family":"Farrington","sequence":"additional","affiliation":[{"name":"Lister Hospital , Stevenage , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7652-1572","authenticated-orcid":false,"given":"Philip A","family":"Kalra","sequence":"additional","affiliation":[{"name":"Salford Royal NHS Foundation Trust , Salford , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0745-3478","authenticated-orcid":false,"given":"David C","family":"Wheeler","sequence":"additional","affiliation":[{"name":"University College London , London , UK"},{"name":"George Institute for Global Health , Sydney , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0224-8726","authenticated-orcid":false,"given":"Charles R V","family":"Tomson","sequence":"additional","affiliation":[{"name":"Freeman Hospital , Newcastle upon Tyne , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Ford","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics, University of Glasgow , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6317-3975","authenticated-orcid":false,"given":"John J V","family":"McMurray","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Research Centre, University of Glasgow , 126 University Place, Glasgow G12 8TA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain C","family":"Macdougall","sequence":"additional","affiliation":[{"name":"Department of Renal Medicine, King\u2019s College Hospital , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the PIVOTAL Investigators and Committees","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,12,7]]},"reference":[{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1161\/01.ATV.0000124892.90999.cb","article-title":"Direct detection and quantification of transition metal ions in human atherosclerotic plaques: evidence for the presence of elevated levels of iron and copper","volume":"24","author":"Stadler","year":"2004","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s10534-013-9632-4","article-title":"Oxidative effect of several intravenous iron complexes in the rat","volume":"26","author":"Bailie","year":"2013","journal-title":"Biometals"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1681\/ASN.2013080838","article-title":"Iron sucrose accelerates early atherogenesis by increasing superoxide production and upregulating adhesion molecules in CKD","volume":"25","author":"Kuo","year":"2014","journal-title":"J Am Soc Nephrol"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1001\/archinte.159.14.1542","article-title":"Iron, atherosclerosis, and ischemic heart disease","volume":"159","author":"de Valk","year":"1999","journal-title":"Arch Intern Med"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"e78930","DOI":"10.1371\/journal.pone.0078930","article-title":"Intravenous iron supplementation practices and short-term risk of cardiovascular events in hemodialysis patients","volume":"8","author":"Kshirsagar","year":"2013","journal-title":"PLoS One"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1056\/NEJMoa1810742","article-title":"Intravenous iron in patients undergoing maintenance hemodialysis","volume":"380","author":"Macdougall","year":"2019","journal-title":"N Engl J Med"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1159\/000493551","article-title":"Randomized trial comparing proactive, high-dose versus reactive, low-dose intravenous iron supplementation in hemodialysis (PIVOTAL): study design and baseline data","volume":"48","author":"Macdougall","year":"2018","journal-title":"Am J Nephrol"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.jacc.2017.12.048","article-title":"2017 cardiovascular and stroke endpoint definitions for clinical trials","volume":"71","author":"Hicks","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/j.0006-341X.2000.00554.x","article-title":"Nonparametric analysis of recurrent events and death","volume":"56","author":"Ghosh","year":"2000","journal-title":"Biometrics"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1046\/j.1523-1755.2003.00860.x","article-title":"Smoking and cardiovascular outcomes in dialysis patients: the United States Renal Data System Wave 2 study","volume":"63","author":"Foley","year":"2003","journal-title":"Kidney Int"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1681\/ASN.2016050560","article-title":"Trends in discharge claims for acute myocardial infarction among patients on dialysis","volume":"28","author":"Shroff","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1016\/j.jacc.2015.04.009","article-title":"Cholesterol metabolism and statin effectiveness in hemodialysis patients","volume":"65","author":"Baigent","year":"2015","journal-title":"J Am Coll Cardiol"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1056\/NEJMoa0907845","article-title":"A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease","volume":"361","author":"Pfeffer","year":"2009","journal-title":"N Engl J Med"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1097\/MIB.0b013e318281f4db","article-title":"Iron deficiency generates secondary thrombocytosis and platelet activation in IBD: the randomized, controlled thromboVIT trial","volume":"19","author":"Kulnigg-Dabsch","year":"2013","journal-title":"Inflamm Bowel Dis"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1056\/NEJM199809173391203","article-title":"Poor long-term survival after acute myocardial infarction among patients on long-term dialysis","volume":"339","author":"Herzog","year":"1998","journal-title":"N Engl J Med"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1056\/NEJMoa1915925","article-title":"Management of coronary disease in patients with advanced kidney disease","volume":"382","author":"Bangalore","year":"2020","journal-title":"N Engl J Med"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1056\/NEJMoa0810177","article-title":"Rosuvastatin and cardiovascular events in patients undergoing hemodialysis","volume":"360","author":"Fellstr\u00f6m","year":"2009","journal-title":"N Engl J Med"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1056\/NEJMoa043545","article-title":"Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis","volume":"353","author":"Wanner","year":"2005","journal-title":"N Engl J Med"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1001\/jamainternmed.2015.6102","article-title":"Representation of patients with kidney disease in trials of cardiovascular interventions: an updated systematic review","volume":"176","author":"Konstantinidis","year":"2016","journal-title":"JAMA Intern Med"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"502","DOI":"10.7326\/M14-0746","article-title":"Role of troponin in patients with chronic kidney disease and suspected acute coronary syndrome: a systematic review","volume":"161","author":"Stacy","year":"2014","journal-title":"Ann Intern Med"},{"key":"2023031717461008100_","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1161\/CIRCULATIONAHA.107.696765","article-title":"Clinical characteristics of dialysis patients with acute myocardial infarction in the United States: a collaborative project of the United States Renal Data System and the National Registry of Myocardial Infarction","volume":"116","author":"Herzog","year":"2007","journal-title":"Circulation"}],"container-title":["Cardiovascular Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cardiovascres\/advance-article-pdf\/doi\/10.1093\/cvr\/cvab317\/42416836\/cvab317.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article-pdf\/119\/1\/213\/49554521\/cvab317.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article-pdf\/119\/1\/213\/49554521\/cvab317.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T19:38:15Z","timestamp":1699558695000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article\/119\/1\/213\/6454738"}},"subtitle":[],"editor":[{"given":"Charalambos","family":"Antoniades","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,12,7]]},"references-count":21,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12,7]]},"published-print":{"date-parts":[[2023,3,17]]}},"URL":"https:\/\/doi.org\/10.1093\/cvr\/cvab317","relation":{},"ISSN":["0008-6363","1755-3245"],"issn-type":[{"value":"0008-6363","type":"print"},{"value":"1755-3245","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,1,1]]},"published":{"date-parts":[[2021,12,7]]}}}