{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T01:01:26Z","timestamp":1794013286570,"version":"4.8.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"42","license":[{"start":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T00:00:00Z","timestamp":1597968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Sanofi and Regeneron Pharmaceuticals, Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Statins reduce cardiovascular risk in patients with acute coronary syndrome (ACS) and normal-to-moderately impaired renal function. It is not known whether proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors provide similar benefit across a range of renal function. We determined whether effects of the PCSK9 inhibitor alirocumab to reduce cardiovascular events and death after ACS are influenced by renal function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>ODYSSEY OUTCOMES compared alirocumab with placebo in patients with recent ACS and dyslipidaemia despite intensive statin treatment. Estimated glomerular filtration rate (eGFR) &amp;lt;30\u2009mL\/min\/1.73 m2 was exclusionary. In 18 918 patients, baseline eGFR was 82.8\u2009\u00b1\u200917.6\u2009mL\/min\/1.73 m2, and low-density lipoprotein cholesterol (LDL-C) was 92\u2009\u00b1\u200931\u2009mg\/dL. At 36\u2009months, alirocumab decreased LDL-C by 48.5% vs. placebo but did not affect eGFR (P\u2009=\u20090.65). Overall, alirocumab reduced risk of the primary outcome (coronary heart disease death, non-fatal myocardial infarction, ischaemic stroke, or unstable angina requiring hospitalization) with fewer deaths. There was no interaction between continuous eGFR and treatment on the primary outcome or death (P\u2009=\u20090.14 and 0.59, respectively). Alirocumab reduced primary outcomes in patients with eGFR \u226590\u2009mL\/min\/1.73 m2 (n\u2009=\u20097470; hazard ratio 0.784, 95% confidence interval 0.670\u20130.919; P\u2009=\u20090.003) and 60 to &amp;lt;90 (n\u2009=\u20099326; 0.833, 0.731\u20130.949; P\u2009=\u20090.006), but not in those with eGFR\u2009&amp;lt;\u200960 (n\u2009=\u20092122; 0.974, 0.805\u20131.178; P\u2009=\u20090.784). Adverse events other than local injection-site reactions were similar in both groups across all categories of eGFR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients with recent ACS, alirocumab was associated with fewer cardiovascular events and deaths across the range of renal function studied, with larger relative risk reductions in those with eGFR\u2009&amp;gt;\u200960\u2009mL\/min\/1.73 m2.<\/jats:p>\n                    <jats:p\/>\n                  <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehaa498","type":"journal-article","created":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T15:26:56Z","timestamp":1590766016000},"page":"4114-4123","source":"Crossref","is-referenced-by-count":77,"title":["Effect of alirocumab on major adverse cardiovascular events according to renal function in patients with a recent acute coronary syndrome: prespecified analysis from the ODYSSEY OUTCOMES randomized clinical trial"],"prefix":"10.1093","volume":"41","author":[{"given":"Jos\u00e9","family":"Tu\u00f1\u00f3n","sequence":"first","affiliation":[{"name":"Division of Cardiology, Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Aut\u00f3noma University, and CIBER CV , Avenida Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe Gabriel","family":"Steg","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Universit\u00e9 de Paris, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, Universit\u00e9 de Paris, FACT (French Alliance for Cardiovascular Trials), INSERM U1148 , Paris, France"},{"name":"National Heart and Lung Institute, Imperial College, Royal Brompton Hospital , London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1278-6245","authenticated-orcid":false,"given":"Deepak L","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9456-850X","authenticated-orcid":false,"given":"Vera A","family":"Bittner","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Disease, University of Alabama at Birmingham , Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"D\u00edaz","sequence":"additional","affiliation":[{"name":"Cardiology Department, Estudios Cl\u00ednicos Latinoam\u00e9rica, Instituto Cardiovascular de Rosario, Rosario, Argentina; Canadian VIGOUR Centre, University of Alberta , Edmonton, AB, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8068-2440","authenticated-orcid":false,"given":"Shaun G","family":"Goodman","sequence":"additional","affiliation":[{"name":"Division of Cardiology, St. Michael\u2019s Hospital, University of Toronto , Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Wouter","family":"Jukema","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Leiden University Medical Center , Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7590-574X","authenticated-orcid":false,"given":"Yong-Un","family":"Kim","sequence":"additional","affiliation":[{"name":"R & D clinical Development, Sanofi , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian H","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Sciences-Cardiovascular & Metabolism Therapeutics, Regeneron Pharmaceuticals , Tarrytown, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1120-6405","authenticated-orcid":false,"given":"Christian","family":"Mueller","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Parkhomenko","sequence":"additional","affiliation":[{"name":"Institute of Cardiology , Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8001-6795","authenticated-orcid":false,"given":"Robert","family":"Pordy","sequence":"additional","affiliation":[{"name":"Clinical Sciences-Cardiovascular & Metabolism Therapeutics, Regeneron Pharmaceuticals , Tarrytown, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piyamitr","family":"Sritara","sequence":"additional","affiliation":[{"name":"Department of Medicine, Ramathibodi Hospital , Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0046-0264","authenticated-orcid":false,"given":"Michael","family":"Szarek","sequence":"additional","affiliation":[{"name":"State University of New York, Downstate School of Public Health , Brooklyn, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7712-6750","authenticated-orcid":false,"given":"Harvey D","family":"White","sequence":"additional","affiliation":[{"name":"Green Lane Cardiovascular Services Auckland City Hospital , Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas M","family":"Zeiher","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Goethe University , Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory G","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of Colorado School of Medicine , Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the ODYSSEY OUTCOMES Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,8,21]]},"reference":[{"key":"2022102510424645600_ehaa498-B1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0140-6736(13)60595-4","article-title":"Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention","volume":"382","author":"Gansevoort","year":"2013","journal-title":"Lancet"},{"key":"2022102510424645600_ehaa498-B2","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.1093\/eurheartj\/ehw272","article-title":"2016 ESC\/EAS guidelines for the management of dyslipidaemias","volume":"37","author":"Catapano","year":"2016","journal-title":"Eur Heart J"},{"key":"2022102510424645600_ehaa498-B3","first-page":"e1082","article-title":"2018 AHA\/ACC\/AACVPR\/AAPA\/ABC\/ACPM\/ADA\/AGS\/APhA\/ASPC\/NLA\/PCNA Guideline on the management of blood cholesterol: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"139","author":"Grundy","year":"2019","journal-title":"Circulation"},{"key":"2022102510424645600_ehaa498-B4","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/ki.2011.178","article-title":"Novel inflammatory mechanisms of accelerated atherosclerosis in kidney disease","volume":"80","author":"Swaminathan","year":"2011","journal-title":"Kidney Int"},{"key":"2022102510424645600_ehaa498-B5","first-page":"94","article-title":"Uremic bleeding: pathogenesis and therapy","volume":"316","author":"Weigert","year":"1998","journal-title":"Am J Med Sci"},{"key":"2022102510424645600_ehaa498-B6","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.2215\/CJN.01930408","article-title":"Accelerated atherosclerotic calcification and Monckeberg\u2019s sclerosis: a continuum of advanced vascular pathology in chronic kidney disease","volume":"3","author":"McCullough","year":"2008","journal-title":"Clin J Am Soc Nephrol"},{"key":"2022102510424645600_ehaa498-B7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.phrs.2013.03.007","article-title":"Statins decrease all-cause mortality only in CKD patients not requiring dialysis therapy\u2014a meta-analysis of 11 randomized controlled trials involving 21,295 participants","volume":"72","author":"Barylski","year":"2013","journal-title":"Pharmacol Res"},{"key":"2022102510424645600_ehaa498-B8","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":"2022102510424645600_ehaa498-B9","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1056\/NEJMoa0810177","article-title":"Rosuvastatin and cardiovascular events in patients undergoing hemodialysis","volume":"360","author":"Fellstrom","year":"2009","journal-title":"N Engl J Med"},{"key":"2022102510424645600_ehaa498-B10","doi-asserted-by":"crossref","first-page":"182","DOI":"10.7326\/M13-2453","article-title":"Lipid management in chronic kidney disease: synopsis of the Kidney Disease: improving Global Outcomes 2013 clinical practice guideline","volume":"160","author":"Tonelli","year":"2014","journal-title":"Ann Intern Med"},{"key":"2022102510424645600_ehaa498-B11","article-title":"2019 ESC\/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk","author":"Mach","year":"2019","journal-title":"Eur Heart J"},{"key":"2022102510424645600_ehaa498-B12","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1056\/NEJMoa1801174","article-title":"Alirocumab and cardiovascular outcomes after acute coronary syndrome","volume":"379","author":"Schwartz","year":"2018","journal-title":"N Engl J Med"},{"key":"2022102510424645600_ehaa498-B13","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1615664","article-title":"Evolocumab and clinical outcomes in patients with cardiovascular disease","volume":"376","author":"Sabatine","year":"2017","journal-title":"N Engl J Med"},{"key":"2022102510424645600_ehaa498-B14","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.kint.2017.12.011","article-title":"Efficacy and safety of lipid lowering by alirocumab in chronic kidney disease","volume":"93","author":"Toth","year":"2018","journal-title":"Kidney Int"},{"key":"2022102510424645600_ehaa498-B15","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.1016\/j.jacc.2019.03.513","article-title":"Efficacy and safety of evolocumab in chronic kidney disease in the FOURIER trial","volume":"73","author":"Charytan","year":"2019","journal-title":"J Am Coll Cardiol"},{"key":"2022102510424645600_ehaa498-B16","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.ahj.2014.07.028","article-title":"Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial","volume":"168","author":"Schwartz","year":"2014","journal-title":"Am Heart J"},{"key":"2022102510424645600_ehaa498-B17","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann Intern Med"},{"key":"2022102510424645600_ehaa498-B18","doi-asserted-by":"publisher","first-page":"CD007784","DOI":"10.1002\/14651858.CD007784.pub2","article-title":"HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis","author":"Palmer","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"2022102510424645600_ehaa498-B19","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S2213-8587(16)30156-5","article-title":"Impact of renal function on the effects of LDL cholesterol lowering with statin-based regimens: a meta-analysis of individual participant data from 28 randomised trials","volume":"4","year":"2016","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2022102510424645600_ehaa498-B20","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1056\/NEJMoa1501031","article-title":"Efficacy and safety of alirocumab in reducing lipids and cardiovascular events","volume":"372","author":"Robinson","year":"2015","journal-title":"N Engl J Med"},{"key":"2022102510424645600_ehaa498-B21","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1159\/000337821","article-title":"Lipid disorders in uremia and dialysis","volume":"178","author":"Bakris","year":"2012","journal-title":"Contrib Nephrol"},{"key":"2022102510424645600_ehaa498-B22","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/S2213-8587(19)30158-5","article-title":"ODYSSEY OUTCOMES Committee Investigators. Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial","volume":"7","author":"Ray","year":"2019","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2022102510424645600_ehaa498-B23","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.jacc.2019.03.013","article-title":"Alirocumab in patients with polyvascular disease and recent acute coronary syndrome: ODYSSEY OUTCOMES trial","volume":"74","author":"Jukema","year":"2019","journal-title":"J Am Coll Cardiol"},{"key":"2022102510424645600_ehaa498-B24","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/j.jacc.2019.07.015","article-title":"Odyssey Outcomes Committees Investigators. Effects of alirocumab on cardiovascular events after coronary bypass surgery","volume":"74","author":"Goodman","year":"2019","journal-title":"J Am Coll Cardiol"},{"key":"2022102510424645600_ehaa498-B25","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1016\/S0140-6736(10)60674-5","article-title":"Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis","volume":"375","author":"Matsushita","year":"2010","journal-title":"Lancet"}],"container-title":["European Heart Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/eurheartj\/article-pdf\/41\/42\/4114\/46618758\/ehaa498.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurheartj\/article-pdf\/41\/42\/4114\/46618758\/ehaa498.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T06:44:25Z","timestamp":1666680265000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurheartj\/article\/41\/42\/4114\/5895197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,21]]},"references-count":25,"journal-issue":{"issue":"42","published-online":{"date-parts":[[2020,8,21]]},"published-print":{"date-parts":[[2020,11,7]]}},"URL":"https:\/\/doi.org\/10.1093\/eurheartj\/ehaa498","relation":{},"ISSN":["0195-668X","1522-9645"],"issn-type":[{"value":"0195-668X","type":"print"},{"value":"1522-9645","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,11,7]]},"published":{"date-parts":[[2020,8,21]]}}}