{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T08:41:07Z","timestamp":1793868067745,"version":"4.6.1"},"reference-count":19,"publisher":"American Medical Association (AMA)","issue":"23","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2024,12,17]]},"abstract":"\n Importance<\/jats:title>\n Elevated lipoprotein(a) increases the risk of atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the effects of zerlasiran, a small-interfering RNA targeting hepatic synthesis of apolipoprotein(a), on lipoprotein(a) serum concentration.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n A multicenter trial in patients with stable ASCVD with serum lipoprotein(a) concentrations greater than or equal to 125 nmol\/L at 26 sites in Europe and South Africa between January 3, 2023, and April 27, 2023, with last follow-up on July 1, 2024.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Participants randomized to receive a subcutaneous dose of placebo every 16 weeks for 3 doses (n\u2009=\u200923) or every 24 weeks for 2 doses (n\u2009=\u200924) or zerlasiran 450 mg every 24 weeks for 2 doses (n\u2009=\u200945), 300 mg every 16 weeks for 3 doses (n\u2009=\u200942), or 300 mg every 24 weeks for 2 doses (n\u2009=\u200944).<\/jats:p>\n <\/jats:sec>\n \n Main Outcome and Measures<\/jats:title>\n The primary outcome was the time-averaged percent change in lipoprotein(a) concentration from baseline to 36 weeks, with follow-up to 60 weeks.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Among 178 patients, mean (SD) age was 63.7 (9.4) years, 46 (25.8%) were female, with a median (IQR) baseline lipoprotein(a) concentration of 213 (177-282) nmol\/L; 172 patients completed the trial. Compared with the pooled placebo group, the least-squares mean time-averaged percent change in lipoprotein(a) concentration from baseline to week 36 was \u221285.6% (95% CI, \u221290.9% to \u221280.3%), \u221282.8% (95% CI, \u221288.2% to \u221277.4%), and \u221281.3% (95% CI, \u221286.7% to \u221276.0%) for the 450 mg every 24 weeks, 300 mg every 16 weeks, and 300 mg every 24 weeks groups, respectively. Median (IQR) percent change in lipoprotein(a) concentration at week 36 was \u221294.5% (\u221297.3% to \u221284.2%) for the 450 mg every 24 weeks group, \u221296.4% (\u221297.7% to \u221292.3%) for the 300 mg every 16 weeks group, and \u221290.0% (\u221293.7% to \u221281.3%) for the 300 mg every 24 weeks group. The most common treatment-related adverse effects were injection site reactions, with mild pain occurring in 2.3% to 7.1% of participants in the first day following drug administration. There were 20 serious adverse events in 17 patients, none considered related to the study drug.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Zerlasiran was well-tolerated and reduced time-averaged lipoprotein(a) concentration by more than 80% during 36 weeks of treatment in patients with ASCVD.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT05537571<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jama.2024.21957","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T15:30:31Z","timestamp":1731943831000},"page":"1992","source":"Crossref","is-referenced-by-count":167,"title":["Zerlasiran\u2014A Small-Interfering RNA Targeting Lipoprotein(a)"],"prefix":"10.1001","volume":"332","author":[{"given":"Steven E.","family":"Nissen","sequence":"first","affiliation":[{"name":"Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Nicholls","sequence":"additional","affiliation":[{"name":"Victorian Heart Institute, Monash University, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann Marie","family":"Navar","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kausik K.","family":"Ray","sequence":"additional","affiliation":[{"name":"Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory G.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine, Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Szarek","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine, Aurora"},{"name":"State University of New York, Downstate Health Sciences University, Brooklyn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik S. G.","family":"Stroes","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Troquay","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Interventional Cardiology, VieCuri Medical Center Northern Limburg, Venray, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannick A. 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