{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T11:26:30Z","timestamp":1794137190084,"version":"4.8.0"},"reference-count":8,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"<jats:sec id=\"ab-hbr240022-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Lipoprotein(a) (Lp[a]) is thought to be the major carrier of oxidized phospholipids (OxPL). OxPL are believed to be a potent driver of inflammation and atherosclerosis. Olpasiran, a small interfering RNA, blocks Lp(a) production by inducing degradation of apolipoprotein(a) messenger RNA. Olpasiran\u2019s effects on OxPL and systemic markers of inflammation are not well described.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hbr240022-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the effects of olpasiran on OxPL, high-sensitivity interleukin 6 (hs-IL-6), and hs-C-reactive protein (hs-CRP) in the OCEAN(a)-DOSE randomized clinical trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hbr240022-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>OCEAN(a)-DOSE was an international, multicenter, placebo-controlled, phase 2, dose-finding randomized clinical trial conducted between July 2020 and November 2022. A total of 281 patients with atherosclerotic cardiovascular disease and Lp(a) levels greater than 150 nmol\/L were included.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hbr240022-7\">\n                    <jats:title>Intervention<\/jats:title>\n                    <jats:p>Participants were randomized to receive 1 of 4 active subcutaneous doses of olpasiran vs placebo: (1) 10 mg, administered every 12 weeks (Q12W); (2) 75 mg, Q12W; (3) 225 mg, Q12W; or (4) 225 mg, administered every 24 weeks (Q24W). OxPL on apolipoprotein B (OxPL-apoB), hs-CRP, and hs-IL-6 were assessed at baseline, week 36, and week 48 in 272 patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hbr240022-8\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>The primary outcome was placebo-adjusted change in OxPL-apoB from baseline to week 36.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hbr240022-9\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 272 participants, median (IQR) age was 62 years (56-69), and 86 participants (31.6%) were female. Baseline median (IQR) Lp(a) concentration was 260.3 nmol\/L (198.1-352.4) and median (IQR) OxPL-apoB concentration was 26.5 nmol\/L (19.7-33.9). The placebo-adjusted mean percentage change in OxPL-apoB from baseline to week 36 was \u221251.6% (95% CI, \u221264.9% to \u221238.2%) for the 10-mg Q12W dose, \u221289.7% (95% CI, \u2212103.0% to \u221276.4%) for the 75-mg Q12W dose, \u221292.3% (95% CI, \u2212105.6% to \u221278.9%) for the 225-mg Q12W dose, and \u221293.7% (95% CI, \u2212107.1% to \u221280.3%) for the Q24W dose (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001 for all). These effects were maintained to week 48 (\u221250.8%, \u2212100.2%, \u2212104.7%, and \u221285.8%, respectively;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001 for all). There was a strong correlation between percentage reduction in Lp(a) and OxPL-apoB for patients treated with olpasiran (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.79;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001). Olpasiran did not significantly impact hs-CRP or hs-IL-6 compared with placebo to weeks 36 or 48 (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;gt;\u2009.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hbr240022-10\">\n                    <jats:title>Conclusion and Relevance<\/jats:title>\n                    <jats:p>In the OCEAN(a)-DOSE multicenter randomized clinical trial, olpasiran led to a significant and sustained reduction in OxPL-apoB but no significant effects on hs-CRP or hs-IL-6.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamacardio.2024.5433","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T11:01:10Z","timestamp":1739358070000},"page":"482","source":"Crossref","is-referenced-by-count":49,"title":["Olpasiran, Oxidized Phospholipids, and Systemic Inflammatory Biomarkers"],"prefix":"10.1001","volume":"10","author":[{"given":"Robert S.","family":"Rosenson","sequence":"first","affiliation":[{"name":"Metabolism and Lipids Program, Icahn School of Medicine, Mount Sinai Hospital, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Antonio G.","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Global Development, Amgen, Thousand Oaks, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Gaudet","sequence":"additional","affiliation":[{"name":"Department of Medicine, Universit\u00e9 de Montr\u00e9al, Chicoutimi, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth J.","family":"Baum","sequence":"additional","affiliation":[{"name":"Flourish Research, Boca Raton, Florida"},{"name":"Charles E Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elmer","family":"Stout","sequence":"additional","affiliation":[{"name":"Crossroads Clinical Research Inc, Mooresville, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman E.","family":"Lepor","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine, University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong-Gun","family":"Park","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina A.","family":"Murphy","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beat","family":"Knusel","sequence":"additional","affiliation":[{"name":"Global Development, Amgen, Thousand Oaks, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingying","family":"Wang","sequence":"additional","affiliation":[{"name":"Global Development, Amgen, Thousand Oaks, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomaz","family":"Wilmanski","sequence":"additional","affiliation":[{"name":"Global Development, Amgen, Thousand Oaks, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huei","family":"Wang","sequence":"additional","affiliation":[{"name":"Global Development, Amgen, Thousand Oaks, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Wu","sequence":"additional","affiliation":[{"name":"Global Development, Amgen, Thousand Oaks, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helina","family":"Kassahun","sequence":"additional","affiliation":[{"name":"Global Development, Amgen, Thousand Oaks, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc S.","family":"Sabatine","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"O\u2019Donoghue","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"OCEAN(a)-DOSE Trial Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"3","key":"hbr240022r1","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1038\/s41569-023-00937-4","article-title":"Oxidized phospholipids in cardiovascular disease.","volume":"21","author":"Tsimikas","year":"2024","journal-title":"Nat Rev Cardiol"},{"issue":"20","key":"hbr240022r2","doi-asserted-by":"publisher","first-page":"1855","DOI":"10.1056\/NEJMoa2211023","article-title":"Small interfering RNA to 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