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Similar questions were raised regarding proprotein convertase subtilisin\/kexin\u2010type 9 inhibitors (<jats:styled-content style=\"fixed-case\">PCSK9i<\/jats:styled-content>) and neurocognitive function. No prospectively designed study has evaluated the relationship between long\u2010term <jats:styled-content style=\"fixed-case\">PCSK9i<\/jats:styled-content> use and cognition changes. Patients with prior cardiovascular disease treated with maximally tolerated statin enrolled in <jats:styled-content style=\"fixed-case\">FOURIER<\/jats:styled-content> (the randomized, double\u2010blind, placebo\u2010controlled cardiovascular outcome study of the <jats:styled-content style=\"fixed-case\">PCSK9i<\/jats:styled-content> evolocumab) could participate in this prospective assessment of cognitive function (<jats:styled-content style=\"fixed-case\">EBBINGHAUS<\/jats:styled-content>). Key additional exclusion criteria for <jats:styled-content style=\"fixed-case\">EBBINGHAUS<\/jats:styled-content> were dementia, cognitive impairment, or other significant mental or neurological disorder. Cognitive testing was performed using the Cambridge Neuropsychological Test Automated Battery, a tablet\u2010based tool assessing executive function, working memory, memory function, and psychomotor speed at baseline, weeks 24 and 48, every 48 weeks thereafter, and study end. The primary endpoint was spatial working memory strategy index of executive function (<jats:styled-content style=\"fixed-case\">SWMSI<\/jats:styled-content>). The primary hypothesis was that evolocumab would be noninferior to placebo in the mean change from baseline over time in <jats:styled-content style=\"fixed-case\">SWMSI<\/jats:styled-content>. Fifteen hundred cognitively normal patients completing the assessments provided approximately 97% power to demonstrate that the upper 95% confidence interval for the treatment difference in mean change from baseline in <jats:styled-content style=\"fixed-case\">SWMSI<\/jats:styled-content> over time is &lt;20% of the <jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content> of the mean change in the placebo group. An exploratory analysis will compare neurocognitive function in patients with post\u2010baseline low\u2010density lipoprotein cholesterol &lt;25 mg\/<jats:styled-content style=\"fixed-case\">dL<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">EBBINGHAUS<\/jats:styled-content> will evaluate whether the addition of evolocumab to statin therapy affects cognitive function over time in patients with stable cardiovascular disease.<\/jats:p>","DOI":"10.1002\/clc.22678","type":"journal-article","created":{"date-parts":[[2017,2,16]],"date-time":"2017-02-16T16:02:41Z","timestamp":1487260961000},"page":"59-65","source":"Crossref","is-referenced-by-count":56,"title":["Design and rationale of the <scp>EBBINGHAUS<\/scp> trial: A phase 3, double\u2010blind, placebo\u2010controlled, multicenter study to assess the effect of evolocumab on cognitive function in patients with clinically evident cardiovascular disease and receiving statin background lipid\u2010lowering therapy\u2014A cognitive study of patients enrolled in the <scp>FOURIER<\/scp> trial"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4110-7675","authenticated-orcid":false,"given":"Robert P.","family":"Giugliano","sequence":"first","affiliation":[{"name":"TIMI Study Group, Brigham and Women's Hospital  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Mach","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Cantonal Hospital Geneva University Hospitals  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenton","family":"Zavitz","sequence":"additional","affiliation":[{"name":"Cambridge Cognition  Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Kurtz","sequence":"additional","affiliation":[{"name":"Amgen  Thousand Oaks California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Schneider","sequence":"additional","affiliation":[{"name":"Amgen  Thousand Oaks California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huei","family":"Wang","sequence":"additional","affiliation":[{"name":"Amgen  Thousand Oaks California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Keech","sequence":"additional","affiliation":[{"name":"NHMRC Clinical Trials Centre, Sydney Medical School the University of Sydney  Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terje R.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Center for Preventive Medicine, Oslo University Hospital, Ullev\u00e5l; and Medical Faculty University of Oslo  Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc S.","family":"Sabatine","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Brigham and Women's Hospital  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Sever","sequence":"additional","affiliation":[{"name":"International Centre for Circulatory Health, Imperial College London  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narimon","family":"Honarpour","sequence":"additional","affiliation":[{"name":"Amgen  Thousand Oaks California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Wasserman","sequence":"additional","affiliation":[{"name":"Amgen  Thousand Oaks California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian R.","family":"Ott","sequence":"additional","affiliation":[{"name":"Department of Neurology the Warren Alpert Medical School of Brown University  Providence Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the EBBINGHAUS Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,16]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.13985"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1410489"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/clc.22577"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/clc.22641"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07474.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(00)00353-3"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2004.07.041"},{"key":"e_1_2_6_9_1","unstructured":"US Food and Drug Administration. 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