{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T10:03:59Z","timestamp":1779789839992,"version":"3.53.1"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp;amp; Metabol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hypertriglyceridemia is a widely prevalent disorder of lipid metabolism that increases the risk of cardiovascular disease and pancreatitis, and it often remains difficult to control even with standard treatments. Olezarsen, an antisense oligonucleotide that targets apolipoprotein C\u2010III (ApoC\u2010III), offers a new and promising option for lowering triglyceride levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic search of PubMed, Scopus, Web of Science, and Cochrane was conducted through September 2025 to identify randomized controlled trials (RCTs) comparing olezarsen with placebo in adults with hypertriglyceridemia at high cardiovascular risk. Dichotomous outcomes were analysed as risk ratios (RRs) and continuous outcomes as percentage mean differences (MDs), both with 95% confidence intervals (CIs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Four RCTs (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091615 patients) were included. Olezarsen significantly reduced triglycerides (MD \u221247.71%, 95% CI \u221256.78 to \u221238.64,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), non\u2010HDL\u2010C (MD \u221222.11%, 95% CI \u221228.48 to \u221215.75,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), ApoC\u2010III (MD \u221268.93%, 95% CI \u221277.54 to \u221260.31,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), VLDL\u2010C (MD \u221248.52%, 95% CI \u221257.16 to \u221239.87,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), and ApoB (MD \u221210.67%, 95% CI \u221216.83 to \u22124.51,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0007), while increasing HDL\u2010C (MD 35.13%, 95% CI \u201327.30 to \u201342.96,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). LDL\u2010C showed no significant change. The risks of any or serious adverse events were comparable to placebo. Olezarsen was associated with fewer acute pancreatitis events (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.035) but higher rates of liver enzyme elevations \u2265\u20093\u00d7 ULN (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.046).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Olezarsen demonstrated consistent improvements in triglycerides and other atherogenic lipid parameters with an overall acceptable safety profile. These findings suggest that olezarsen may be a useful adjunct option for patients with persistent hypertriglyceridemia despite standard therapy. Further large\u2010scale and long\u2010term studies are needed to confirm its cardiovascular and safety outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/edm2.70220","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T03:39:44Z","timestamp":1776742784000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Olezarsen in Hypertriglyceridemia With High Cardiac Risk: A\n                    <scp>GRADE<\/scp>\n                    \u2010Assessed Meta\u2010Analysis of Randomized Trials With Trial Sequential Evidence"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2718-8627","authenticated-orcid":false,"given":"Ahmed","family":"Emara","sequence":"first","affiliation":[{"name":"Faculty of Medicine Al\u2010Azhar University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5122-8200","authenticated-orcid":false,"given":"Ameer","family":"Awashra","sequence":"additional","affiliation":[{"name":"Department of Medicine An\u2010Najah National University  Nablus West Bank Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba","family":"Aboeldahab","sequence":"additional","affiliation":[{"name":"Clinical Research Department El\u2010Gomhoria General Hospital, MOHP  Alexandria Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5802-2291","authenticated-orcid":false,"given":"Ahmed Farid","family":"Gadelmawla","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Menoufia University  Menoufia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamza A.","family":"Abdul\u2010Hafez","sequence":"additional","affiliation":[{"name":"Department of Medicine An\u2010Najah National University  Nablus West Bank Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2337-6588","authenticated-orcid":false,"given":"Abdullah M.","family":"Alharran","sequence":"additional","affiliation":[{"name":"Arabian Gulf University  Manama Kingdom of Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal A.","family":"Alsubaiei","sequence":"additional","affiliation":[{"name":"Kuwait Institute for Medical Specializations  Kuwait City Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muneera Jasim","family":"AlRumaihi","sequence":"additional","affiliation":[{"name":"Arabian Gulf University  Manama Kingdom of Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Ahmed","family":"Albuhmaid","sequence":"additional","affiliation":[{"name":"Arabian Gulf University  Manama Kingdom of Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8300-0262","authenticated-orcid":false,"given":"Abdalhakim","family":"Shubietah","sequence":"additional","affiliation":[{"name":"Department of Medicine Advocate Illinois Masonic Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.06.011"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab551"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.041998"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210\u2010025\u201004406\u20102"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnab037"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2024.2408369"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11883\u2010025\u201001345\u20104"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2402309"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1307095"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/MS9.0000000000003505"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.37616\/2212\u20105043.1439"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781119536604"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13643\u2010016\u20100384\u20104"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39489.470347"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/ebmental\u20102019\u2010300117"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2007.10.007"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12874\u2010017\u20100315\u20107"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2400201"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2507227"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab820"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2404143"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2404147"},{"key":"e_1_2_15_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2025.156187"},{"key":"e_1_2_15_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2023.100475"},{"key":"e_1_2_15_28_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2024.0959"},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.12997\/jla.2025.14.3.247"},{"key":"e_1_2_15_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2025.02.035"},{"key":"e_1_2_15_31_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2409368"},{"key":"e_1_2_15_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1715944"},{"key":"e_1_2_15_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.70316"}],"container-title":["Endocrinology, Diabetes &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/edm2.70220","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/edm2.70220","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/edm2.70220","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T09:18:57Z","timestamp":1779787137000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/edm2.70220"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":32,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/edm2.70220"],"URL":"https:\/\/doi.org\/10.1002\/edm2.70220","archive":["Portico"],"relation":{},"ISSN":["2398-9238","2398-9238"],"issn-type":[{"value":"2398-9238","type":"print"},{"value":"2398-9238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,20]]},"assertion":[{"value":"2025-12-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70220"}}