{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T05:06:42Z","timestamp":1776488802847,"version":"3.51.2"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"vor","delay-in-days":239,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T00:00:00Z","timestamp":1595808000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Sanofi and Regeneron Pharmaceuticals, Inc"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,3,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Statins are pivotal to the secondary prevention of major adverse cardiovascular events, but some patients are statin-intolerant. We examined the effects of the proprotein convertase subtilisin\/kexin type 9 (PCSK9) inhibitor alirocumab on the risk of major adverse cardiovascular events according to the intensity of background statin treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>The ODYSSEY OUTCOMES trial compared alirocumab with placebo in 18,924 patients with acute coronary syndrome and dyslipidaemia despite intensive or maximum-tolerated statin treatment (including no statin if intolerance was documented). The primary outcome (major adverse cardiovascular events) comprised coronary heart disease death, non-fatal myocardial infarction, ischaemic stroke, or unstable angina. Median follow-up was 2.8 years. Baseline statin treatment was high-intensity (88.8%), low\/moderate-intensity (8.7%) or none (2.4%). Median baseline low-density lipoprotein cholesterol was 86, 89 and 139\u2009mg\/dL (P\u2009&amp;lt;\u20090.001) in these statin treatment categories, respectively. Alirocumab produced similar relative reductions in low-density lipoprotein cholesterol from baseline across statin treatment subgroups, but the mean absolute reductions differed (52.9, 56.7 and 86.1\u2009mg\/dL, respectively; P\u2009&amp;lt;\u20090.001). With placebo, the incidence of major adverse cardiovascular events was highest in the no statin subgroup (10.8%, 10.7% and 26.0% respectively). Alirocumab reduced major adverse cardiovascular events in each statin subgroup (hazard ratio 0.88, 95% confidence interval (CI) 0.80\u20130.96; 0.68, 0.49\u20130.94; and 0.65, 0.44\u20130.97, respectively; Pinteraction\u2009=\u20090.14) with a gradient of absolute risk reduction: 1.25%, 95% CI 0.34\u20132.16; 3.16%, 0.38\u20135.94; 7.97%, 0.42\u201315.51; Pinteraction\u2009=\u20090.106).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>PCSK9 inhibition with alirocumab reduces the relative risk of major adverse cardiovascular events after acute coronary syndrome irrespective of background statin treatment. However, patients on no statin are at high absolute risk for recurrent major adverse cardiovascular events; alirocumab substantially reduces that risk. PCSK9 inhibition may be an important therapeutic strategy for statin-intolerant patients with acute coronary syndrome.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1177\/2047487320941987","type":"journal-article","created":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T06:04:34Z","timestamp":1595916274000},"page":"33-43","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":47,"title":["Intensity of statin treatment after acute coronary syndrome, residual risk, and its modification by alirocumab: insights from the ODYSSEY OUTCOMES trial"],"prefix":"10.1093","volume":"28","author":[{"given":"Rafael","family":"Diaz","sequence":"first","affiliation":[{"name":"Estudios Cl\u00ednicos Latino Am\u00e9rica, Instituto Cardiovascular de Rosario, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian H","family":"Li","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc., Tarrytown, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepak L","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera A","family":"Bittner","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Disease, University of Alabama at Birmingham, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie T","family":"Baccara-Dinet","sequence":"additional","affiliation":[{"name":"Sanofi R&D, Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaun G","family":"Goodman","sequence":"additional","affiliation":[{"name":"Canadian VIGOUR Centre, University of Alberta, Canada"},{"name":"St Michael\u2019s Hospital, University of Toronto, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J Wouter","family":"Jukema","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Leiden University Medical Center, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Kimura","sequence":"additional","affiliation":[{"name":"Kyoto University, Graduate School of Medicine, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Parkhomenko","sequence":"additional","affiliation":[{"name":"MD Strazhesko Institute of Cardiology, AMS of Ukraine, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Pordy","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc., Tarrytown, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u017deljko","family":"Reiner","sequence":"additional","affiliation":[{"name":"University Hospital Center Zagreb, University of Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew T","family":"Roe","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University Medical Center, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Szarek","sequence":"additional","affiliation":[{"name":"State University of New York, Downstate School of Public Health, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hung-Fat","family":"Tse","sequence":"additional","affiliation":[{"name":"Queen Mary Hospital, Hong Kong, Special Administrative Region of the People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harvey D","family":"White","sequence":"additional","affiliation":[{"name":"Green Lane Cardiovascular Services, Auckland City Hospital, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doron","family":"Zahger","sequence":"additional","affiliation":[{"name":"Soroka University Medical Center, Ben Gurion University of the Negev, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas M","family":"Zeiher","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Goethe University, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory G","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of Colorado School of Medicine, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ph Gabriel","family":"Steg","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, FACT (French Alliance for Cardiovascular Trials), and INSERM, France"},{"name":"Imperial College, Royal Brompton Hospital, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the ODYSSEY OUTCOMES Committees and Investigators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,7,27]]},"reference":[{"key":"2021070804544465800_zwaa445-bibr1","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1016\/S0140-6736(10)61350-5","article-title":"Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials","volume":"376","author":"Baigent","year":"2010","journal-title":"Lancet"},{"key":"2021070804544465800_zwaa445-bibr2","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nrcardio.2013.80","article-title":"Statins in the primary prevention of cardiovascular disease","volume":"10","author":"Reiner","year":"2013","journal-title":"Nat Rev Cardiol"},{"key":"2021070804544465800_zwaa445-bibr3","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1093\/ehjcvp\/pvy028","article-title":"Reasons for disparity in statin adherence rates between clinical trials and real-world observations: a review","volume":"4","author":"Vonbank","year":"2018","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"key":"2021070804544465800_zwaa445-bibr4","doi-asserted-by":"crossref","first-page":"207","DOI":"10.5551\/jat.RV17030","article-title":"Diagnosis and management of statin intolerance","volume":"26","author":"Alonso","year":"2019","journal-title":"J Atheroscler Thromb"},{"key":"2021070804544465800_zwaa445-bibr5","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1080\/14740338.2017.1238898","article-title":"Statin intolerance \u2013 a question of definition","volume":"16","author":"Algharably","year":"2017","journal-title":"Expert Opin Drug Saf"},{"key":"2021070804544465800_zwaa445-bibr6","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/j.numecd.2014.05.009","article-title":"Resistance and intolerance to statin","volume":"24","author":"Reiner","year":"2014","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"2021070804544465800_zwaa445-bibr7","article-title":"2018 AHA\/ACC\/AACVPR\/AAPA\/ABC\/ACPM\/ADA\/AGS\/APhA\/ASPC \/NLA\/PCNA Guideline on the management of blood cholesterol: executive summary: A Report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","author":"Grundy","journal-title":"Circulation"},{"key":"2021070804544465800_zwaa445-bibr8","author":"Mach"},{"key":"2021070804544465800_zwaa445-bibr9","author":"Rodriguez","year":"2019"},{"key":"2021070804544465800_zwaa445-bibr10","doi-asserted-by":"crossref","first-page":"948","DOI":"10.5414\/CP202132","article-title":"Association between non-adherence to statin and hospitalization for cardiovascular disease and all-cause mortality in a national cohort","volume":"52","author":"Shin","year":"2014","journal-title":"Int J Clin Pharmacol Ther"},{"key":"2021070804544465800_zwaa445-bibr11","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1016\/j.jacc.2017.01.019","article-title":"Statin intolerance: an elusive but morbid disorder","volume":"69","author":"Nissen","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"2021070804544465800_zwaa445-bibr12","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":"2021070804544465800_zwaa445-bibr13","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1001\/jama.2012.25790","article-title":"Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial","volume":"308","author":"Sullivan","year":"2012","journal-title":"JAMA"},{"key":"2021070804544465800_zwaa445-bibr14","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.jacl.2015.08.006","article-title":"Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: the ODYSSEY ALTERNATIVE randomized trial","volume":"9","author":"Moriarty","year":"2015","journal-title":"J Clin Lipidol"},{"key":"2021070804544465800_zwaa445-bibr15","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":"2021070804544465800_zwaa445-bibr16","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":"2021070804544465800_zwaa445-bibr17","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1161\/CIRCULATIONAHA.118.038840","article-title":"Effect of alirocumab on mortality after acute coronary syndromes","volume":"140","author":"Steg","year":"2019","journal-title":"Circulation"},{"key":"2021070804544465800_zwaa445-bibr18","article-title":"Is the novel LDL-cholesterol goal &lt;1.4\u2009mmol\/L achievable without a PCSK9 inhibitor in a chronic coronary population from clinical practice?","author":"Munkhaugen","journal-title":"Eur J Prev Cardiol"},{"key":"2021070804544465800_zwaa445-bibr19","article-title":"Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: a pooled analysis from 10 ODYSSEY phase 3 studies","author":"Mahmood","journal-title":"Eur J Prev Cardiol"},{"key":"2021070804544465800_zwaa445-bibr20","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.atherosclerosis.2016.01.018","article-title":"Lipid lowering drug therapy in patients with coronary heart disease from 24 European countries \u2013 findings from the EUROASPIRE IV survey","volume":"246","author":"Reiner","year":"2016","journal-title":"Atherosclerosis"},{"key":"2021070804544465800_zwaa445-bibr21","author":"Goodman","year":"2020"},{"key":"2021070804544465800_zwaa445-bibr22"},{"key":"2021070804544465800_zwaa445-bibr23","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.atherosclerosis.2018.06.002","article-title":"Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: a randomized, placebo-controlled study","volume":"277","author":"Ballantyne","year":"2018","journal-title":"Atherosclerosis"}],"container-title":["European Journal of Preventive Cardiology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/2047487320941987","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/2047487320941987","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/academic.oup.com\/eurjpc\/article-pdf\/28\/1\/33\/36669612\/zwaa445.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/eurjpc\/article-pdf\/28\/1\/33\/36669612\/zwaa445.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T08:54:57Z","timestamp":1625734497000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjpc\/article\/28\/1\/33\/6182408"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,27]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,7,27]]},"published-print":{"date-parts":[[2021,3,23]]}},"URL":"https:\/\/doi.org\/10.1177\/2047487320941987","relation":{},"ISSN":["2047-4873","2047-4881"],"issn-type":[{"value":"2047-4873","type":"print"},{"value":"2047-4881","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,1,1]]},"published":{"date-parts":[[2020,7,27]]}}}