{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T17:46:17Z","timestamp":1771263977907,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,3,4]],"date-time":"2016-03-04T00:00:00Z","timestamp":1457049600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Cardiology"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Statins are the accepted standard for lowering low\u2010density lipoprotein cholesterol (<jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\u2010C). However, 5% to 10% of statin\u2010treated patients report intolerance, mostly due to muscle\u2010related adverse effects. Challenges exist to objective identification of statin\u2010intolerant patients. Evolocumab is a monoclonal antibody that binds proprotein convertase subtilisin\/kexin type 9 (<jats:styled-content style=\"fixed-case\">PCSK9<\/jats:styled-content>), resulting in marked <jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\u2010C reduction. We report the design of Goal Achievement After Utilizing an Anti\u2010<jats:styled-content style=\"fixed-case\">PCSK9<\/jats:styled-content> Antibody in Statin\u2010Intolerant Subjects 3 (<jats:styled-content style=\"fixed-case\">GAUSS<\/jats:styled-content>\u20103), a phase 3, multicenter, randomized, double\u2010blind, ezetimibe\u2010controlled study to compare effectiveness of 24 weeks of evolocumab 420 mg monthly vs ezetimibe 10 mg daily in hypercholesterolemic patients unable to tolerate an effective statin dose. The study incorporates a novel atorvastatin\u2010controlled, double\u2010blind, crossover phase to objectively identify statin intolerance. Eligible patients had <jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\u2010C above the National Cholesterol Education Project Adult Treatment Panel <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> target level for the appropriate coronary heart disease risk category and were unable to tolerate \u22653 statins or 2 statins (one of which was atorvastatin \u226410 mg\/d) or had a history of marked creatine kinase elevation accompanied by muscle symptoms while on 1 statin. This trial has 2 co\u2010primary endpoints: mean percent change from baseline in <jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\u2010C at weeks 22 and 24 and percent change from baseline in <jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\u2010C at week 24. Key secondary efficacy endpoints include change from baseline in <jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\u2010C, percent of patients attaining <jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\u2010C &lt;70 mg\/<jats:styled-content style=\"fixed-case\">dL<\/jats:styled-content> (1.81 mmol\/L), and percent change from baseline in total cholesterol, non\u2013high\u2010density lipoprotein cholesterol, and apolipoprotein B. Recruitment of 511 patients was completed on November 28, 2014.<\/jats:p>","DOI":"10.1002\/clc.22518","type":"journal-article","created":{"date-parts":[[2016,3,6]],"date-time":"2016-03-06T08:44:57Z","timestamp":1457253897000},"page":"137-144","source":"Crossref","is-referenced-by-count":33,"title":["Comparison of <scp>PCSK9<\/scp> Inhibitor Evolocumab vs Ezetimibe in Statin\u2010Intolerant Patients: Design of the Goal Achievement After Utilizing an Anti\u2010<scp>PCSK9<\/scp> Antibody in Statin\u2010Intolerant Subjects 3 (<scp>GAUSS<\/scp>\u20103) Trial"],"prefix":"10.1002","volume":"39","author":[{"given":"Steven E.","family":"Nissen","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine Cleveland Clinic Foundation  Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo E.","family":"Dent\u2010Acosta","sequence":"additional","affiliation":[{"name":"Department of Clinical Development, and Biostatistics, Amgen Inc.  Thousand Oaks, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert S.","family":"Rosenson","sequence":"additional","affiliation":[{"name":"The Cardiometabolic Disorders Unit, Mount Sinai Heart Icahn School of Medicine at Mount Sinai  New York, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Stroes","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine Academic Medical Center  Amsterdam Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naveed","family":"Sattar","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow  Glasgow United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Preiss","sequence":"additional","affiliation":[{"name":"Clinical Trial Service Unit and Epidemiological Services Unit University of Oxford  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.B. John","family":"Mancini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christie M.","family":"Ballantyne","sequence":"additional","affiliation":[{"name":"Department of Medicine, Baylor College of Medicine and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center  Houston, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberico","family":"Catapano","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences University of Milan, and IRCCS Multimedica  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioanna","family":"Gouni\u2010Berthold","sequence":"additional","affiliation":[{"name":"Center for Endocrinology, Diabetes and Preventive Medicine University of Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evan A.","family":"Stein","sequence":"additional","affiliation":[{"name":"Metabolic and Atherosclerosis Research Center  Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Clinical Development, and Biostatistics, Amgen Inc.  Thousand Oaks, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott M.","family":"Wasserman","sequence":"additional","affiliation":[{"name":"Department of Clinical Development, and Biostatistics, Amgen Inc.  Thousand Oaks, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rob","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Clinical Development, and Biostatistics, Amgen Inc.  Thousand Oaks, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul D.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Cardiology Hartford Hospital  Hartford, Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the GAUSS\u20103 Investigators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,3,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-005-5686-z"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.13.1681"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-158-7-201304020-00004"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv043"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2014.03.004"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.279.18.1458"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1497.2004.30516.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.03.019"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.25790"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2014.12.016"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1K604"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1410489"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1316222"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1501031"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2015.08.006"}],"container-title":["Clinical Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fclc.22518","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/clc.22518","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T09:33:41Z","timestamp":1696584821000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/clc.22518"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3]]},"references-count":15,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["10.1002\/clc.22518"],"URL":"https:\/\/doi.org\/10.1002\/clc.22518","archive":["Portico"],"relation":{},"ISSN":["0160-9289","1932-8737"],"issn-type":[{"value":"0160-9289","type":"print"},{"value":"1932-8737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3]]}}}