Journal of the American Medical Association最新文献

{"title":"Zerlasiran-A Small-Interfering RNA Targeting Lipoprotein(a): A Phase 2 Randomized Clinical Trial.","authors":"Steven E Nissen, Qiuqing Wang, Stephen J Nicholls, Ann Marie Navar, Kausik K Ray, Gregory G Schwartz, Michael Szarek, Erik S G Stroes, Roland Troquay, Jannick A N Dorresteijn, Henry Fok, David A Rider, Steven Romano, Kathy Wolski, Curtis Rambaran","doi":"10.1001/jama.2024.21957","DOIUrl":"10.1001/jama.2024.21957","url":null,"abstract":"<p><strong>Importance: </strong>Elevated lipoprotein(a) increases the risk of atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis.</p><p><strong>Objective: </strong>To evaluate the effects of zerlasiran, a small-interfering RNA targeting hepatic synthesis of apolipoprotein(a), on lipoprotein(a) serum concentration.</p><p><strong>Design, setting, and participants: </strong>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.</p><p><strong>Interventions: </strong>Participants randomized to receive a subcutaneous dose of placebo every 16 weeks for 3 doses (n = 23) or every 24 weeks for 2 doses (n = 24) or zerlasiran 450 mg every 24 weeks for 2 doses (n = 45), 300 mg every 16 weeks for 3 doses (n = 42), or 300 mg every 24 weeks for 2 doses (n = 44).</p><p><strong>Main outcome and measures: </strong>The primary outcome was the time-averaged percent change in lipoprotein(a) concentration from baseline to 36 weeks, with follow-up to 60 weeks.</p><p><strong>Results: </strong>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 -85.6% (95% CI, -90.9% to -80.3%), -82.8% (95% CI, -88.2% to -77.4%), and -81.3% (95% CI, -86.7% to -76.0%) 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 -94.5% (-97.3% to -84.2%) for the 450 mg every 24 weeks group, -96.4% (-97.7% to -92.3%) for the 300 mg every 16 weeks group, and -90.0% (-93.7% to -81.3%) 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.</p><p><strong>Conclusions: </strong>Zerlasiran was well-tolerated and reduced time-averaged lipoprotein(a) concentration by more than 80% during 36 weeks of treatment in patients with ASCVD.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT05537571.</p>","PeriodicalId":17196,"journal":{"name":"Journal of the American Medical Association","volume":" ","pages":"1992-2002"},"PeriodicalIF":0.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare Disease Innovation at the FDA-Opportunities for Implementation.","authors":"Carolyn K Shore, Tequam L Worku, Jeffrey Kahn","doi":"10.1001/jama.2024.20358","DOIUrl":"10.1001/jama.2024.20358","url":null,"abstract":"","PeriodicalId":17196,"journal":{"name":"Journal of the American Medical Association","volume":" ","pages":"1973-1974"},"PeriodicalIF":0.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methadone's Moment.","authors":"Michael A Incze, Caty Simon, Leslie W Suen","doi":"10.1001/jama.2024.19914","DOIUrl":"10.1001/jama.2024.19914","url":null,"abstract":"","PeriodicalId":17196,"journal":{"name":"Journal of the American Medical Association","volume":" ","pages":"1969-1970"},"PeriodicalIF":0.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Symptom Monitoring With Patient-Reported Outcomes During Pediatric Cancer Care.","authors":"Ethan Basch, Allison Barz Leahy, Bryce B Reeve","doi":"10.1001/jama.2024.17371","DOIUrl":"10.1001/jama.2024.17371","url":null,"abstract":"","PeriodicalId":17196,"journal":{"name":"Journal of the American Medical Association","volume":" ","pages":"1979-1980"},"PeriodicalIF":0.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuous vs Intermittent β-Lactam Antibiotic Infusions for Sepsis.","authors":"Jiashu Han, Queran Lin, Dan Shan","doi":"10.1001/jama.2024.23272","DOIUrl":"https://doi.org/10.1001/jama.2024.23272","url":null,"abstract":"","PeriodicalId":17196,"journal":{"name":"Journal of the American Medical Association","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuous vs Intermittent β-Lactam Antibiotic Infusions for Sepsis-Reply.","authors":"Joel M Dulhunty, Jason A Roberts, Jeffrey Lipman","doi":"10.1001/jama.2024.23275","DOIUrl":"10.1001/jama.2024.23275","url":null,"abstract":"","PeriodicalId":17196,"journal":{"name":"Journal of the American Medical Association","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lp(a) Reduction, GLP-1s for Heart Failure, and More-Highlights From the AHA Scientific Sessions.","authors":"Jennifer Abbasi","doi":"10.1001/jama.2024.21051","DOIUrl":"https://doi.org/10.1001/jama.2024.21051","url":null,"abstract":"","PeriodicalId":17196,"journal":{"name":"Journal of the American Medical Association","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Many Acute Care Hospital Infections Drop to Prepandemic Levels.","authors":"Samantha Anderer","doi":"10.1001/jama.2024.24893","DOIUrl":"https://doi.org/10.1001/jama.2024.24893","url":null,"abstract":"","PeriodicalId":17196,"journal":{"name":"Journal of the American Medical Association","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Research Suggests Increased Risk of Some Autoimmune Disorders After COVID-19.","authors":"Samantha Anderer","doi":"10.1001/jama.2024.24894","DOIUrl":"https://doi.org/10.1001/jama.2024.24894","url":null,"abstract":"","PeriodicalId":17196,"journal":{"name":"Journal of the American Medical Association","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant Camrelizumab for Triple-Negative Breast Cancer.","authors":"Heikki Joensuu","doi":"10.1001/jama.2024.25927","DOIUrl":"https://doi.org/10.1001/jama.2024.25927","url":null,"abstract":"","PeriodicalId":17196,"journal":{"name":"Journal of the American Medical Association","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}