{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:42:05Z","timestamp":1790502125936,"version":"4.1.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,2,19]]},"abstract":"\n Background<\/jats:title>\n \n Beyond their potent LDL (low\u2010density lipoprotein) cholesterol (\n LDL<\/jats:styled-content>\n \u2010C)\u2013lowering efficacy (50\u201360%), PCSK9 (proprotein convertase subtilisin\/kexin type 9) inhibitors also reduce Lp(a) (lipoprotein[a]) levels by 25% to 30%, suggesting a 2:1 response ratio. We aimed to characterize the relationship between\n LDL<\/jats:styled-content>\n \u2010C and Lp(a) lowering by evolocumab, a\n PCSK<\/jats:styled-content>\n 9 inhibitor, in a large clinical trial population and to determine the prevalence of concordant\/discordant\n LDL<\/jats:styled-content>\n \u2010C and Lp(a) responses to\n PCSK<\/jats:styled-content>\n 9 inhibition.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Data were analyzed from 4 randomized, 12\u2010week, multicenter, phase 3 evolocumab trials. Patients with familial hypercholesterolemia, nonfamilial hypercholesterolemia, or statin intolerance participated in the trials. The main measure was the degree of concordance or discordance of\n LDL<\/jats:styled-content>\n \u2010C and Lp(a) in response to\n PCSK<\/jats:styled-content>\n 9 inhibition; concordant response was defined as\n LDL<\/jats:styled-content>\n \u2010C reduction >35% and Lp(a) reduction >10%. The study cohort comprised 895 patients (438 female; median age: 59.0 years [interquartile range: 51\u201366 years]). Baseline mean level of\n LDL<\/jats:styled-content>\n \u2010C was 133.6 mg\/dL (SE: 1.7) and median Lp(a) level was 46.4 mg\/dL (interquartile range: 18.4\u201382.4 mg\/dL). A discordant response was observed in 165 (19.7%) patients. With these cutoffs, the prevalence of discordance was higher when considering baseline Lp(a) concentrations >30 mg\/dL (26.5%) or >50 mg\/dL (28.6%).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n We demonstrate high prevalence of discordance in\n LDL<\/jats:styled-content>\n \u2010C and Lp(a) reduction in response to evolocumab, particularly when considering higher baseline Lp(a) concentrations, indicating the possibility of alternative pathways beyond LDLR (\n LDL<\/jats:styled-content>\n receptor)\u2013mediated clearance involved in Lp(a) reduction by evolocumab.\n <\/jats:p>\n <\/jats:sec>\n \n Clinical Trial Registration<\/jats:title>\n \n URL<\/jats:styled-content>\n :\n http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n . Unique identifiers:\n NCT<\/jats:styled-content>\n 01763827,\n NCT<\/jats:styled-content>\n 01763866,\n NCT<\/jats:styled-content>\n 01763905,\n NCT<\/jats:styled-content>\n 01763918.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.118.010932","type":"journal-article","created":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T10:10:52Z","timestamp":1550052652000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":61,"title":["Relationship Between Low\u2010Density Lipoprotein Cholesterol and Lipoprotein(a) Lowering in Response to PCSK9 Inhibition With Evolocumab"],"prefix":"10.1161","volume":"8","author":[{"given":"Michael D.","family":"Shapiro","sequence":"first","affiliation":[{"name":"Knight Cardiovascular Institute Center for Preventive Cardiology Oregon Health & Science University Portland OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Minnier","sequence":"additional","affiliation":[{"name":"Knight Cardiovascular Institute Center for Preventive Cardiology Oregon Health & Science University Portland OR"},{"name":"OHSU\u2010PSU School of Public Health Oregon Health & Science University Portland OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagai","family":"Tavori","sequence":"additional","affiliation":[{"name":"Knight Cardiovascular Institute Center for Preventive Cardiology Oregon Health & Science University Portland OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helina","family":"Kassahun","sequence":"additional","affiliation":[{"name":"Amgen Inc. 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