{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T14:13:31Z","timestamp":1788012811085,"version":"build-2784847793"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":673,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T00:00:00Z","timestamp":1707177600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006400","name":"Alnylam Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006400","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006400","name":"Alnylam Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006400","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>HELIOS-A was a Phase 3, open-label study of vutrisiran, an RNA interference therapeutic, in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy. This analysis evaluated vutrisiran's impact on exploratory cardiac endpoints in HELIOS-A patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Patients were randomized 3:1 to subcutaneous vutrisiran 25\u2009mg every 3\u2009months or intravenous patisiran 0.3\u2009mg\/kg every 3\u2009weeks (reference group) for 18\u2009months. Exploratory cardiac endpoints included change from baseline in N-terminal prohormone of brain-type natriuretic peptide (NT-proBNP) and echocardiographic parameters versus external placebo (APOLLO study). The modified intent-to-treat (mITT) population comprised randomized patients receiving any study drug (n\u2009=\u2009122). A cardiac subpopulation with evidence of cardiac amyloid involvement (n\u2009=\u200940) was prespecified. 99mTc scintigraphy exploratory assessments in a planned vutrisiran-treated cohort at select sites were compared with baseline. At Month 18, vutrisiran demonstrated beneficial effects on NT-proBNP versus external placebo in the mITT and cardiac subpopulations (adjusted geometric mean fold change ratio [95% confidence interval] 0.480 [0.383\u20130.600], p\u2009=\u20099.606\u2009\u00d7\u200910\u221210 and 0.491 [0.337\u20130.716], p\u2009=\u20090.0004, respectively). Benefits or trends towards benefit in echocardiographic parameters versus external placebo were observed for both populations. In 99mTc scintigraphy assessments, 32\/47 (68.1%) and 31\/48 (64.6%) patients exhibited reduced normalized left ventricular total uptake and heart-to-contralateral lung ratio, respectively. Perugini grade was reduced or unchanged versus baseline in 55\/57 (96.5%) evaluable patients. No increase in cardiac adverse events was observed with vutrisiran versus external placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Vutrisiran demonstrated evidence of potential benefit on cardiac manifestations in patients with ATTRv amyloidosis with polyneuropathy, with an acceptable safety profile.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.3138","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T02:14:46Z","timestamp":1707272086000},"page":"397-410","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Impact of Vutrisiran on Exploratory Cardiac Parameters in Hereditary Transthyretin-Mediated Amyloidosis with Polyneuropathy"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5470-2257","authenticated-orcid":false,"given":"Pablo","family":"Garcia-Pavia","sequence":"first","affiliation":[{"name":"Department of Cardiology, Hospital Universitario Puerta de Hierro , Madrid ,","place":["Spain"]},{"name":"Centro Nacional de Investigaciones Cardiovasculares (CNIC) , Madrid ,","place":["Spain"]},{"name":"Universidad Francisco de Vitoria (UFV) , Pozuelo de Alarcon ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Grogan","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, Mayo Clinic , Rochester, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parag","family":"Kale","sequence":"additional","affiliation":[{"name":"Center for Advanced Heart and Lung Disease, Baylor University Medical Center , Dallas, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1768-2373","authenticated-orcid":false,"given":"John L.","family":"Berk","sequence":"additional","affiliation":[{"name":"Amyloidosis Center, Boston Medical Center, Boston University , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathew S.","family":"Maurer","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Center for Advanced Cardiac Care, Columbia University Irving Medical Center , New York, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0934-9631","authenticated-orcid":false,"given":"Isabel","family":"Concei\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"Centro Hospitalar Universit\u00e1rio Lisboa Norte, Hospital de Santa Maria and Faculdade de Medicina , Lisbon ,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Di Carli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongshu","family":"Chen","sequence":"additional","affiliation":[{"name":"Alnylam Pharmaceuticals , Cambridge, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Yureneva","sequence":"additional","affiliation":[{"name":"Alnylam Pharmaceuticals , Cambridge, MA 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