{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:00:41Z","timestamp":1790870441211,"version":"4.1.0"},"reference-count":21,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006400","name":"Alnylam Pharmaceuticals, Inc","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006400","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Sex differences in transthyretin cardiac amyloidosis (ATTR-CM) are increasingly recognized; however, women are underrepresented in trials and sex-specific treatment effects remain incompletely understood. We evaluated sex differences in baseline phenotype, outcomes, and vutrisiran response in ATTR-CM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>HELIOS-B was a Phase 3, randomized, double-blind, placebo-controlled trial enrolling patients with wild-type or variant ATTR-CM, randomized 1:1 to receive subcutaneous vutrisiran (25\u2005mg every 12 weeks) or placebo. This prespecified analysis assessed baseline characteristics, efficacy, and safety according to sex.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 654 participants, 49 (7.5%) were women. Variant ATTR-CM was more prevalent in women (42.9% vs 9.1%, P &amp;lt; .001). At baseline, women had smaller absolute left ventricular dimensions and wall thicknesses (P &amp;lt; .05), but when indexed to body surface area, wall thicknesses were higher. Women demonstrated better systolic function, but worse 6-minute walk distances and quality-of-life scores. Vutrisiran reduced the primary composite endpoint of all-cause mortality and recurrent cardiovascular events in both sexes (women, HR 0.59, 95% CI 0.26\u20131.30; men, HR 0.71, 95% CI 0.54\u20130.94; P-interaction = .66). Confidence intervals were wide in women, reflecting limited precision from small subgroup size. Mortality reduction was observed in both sexes (HR 0.56, 95% CI 0.14\u20132.34 in women, HR 0.65, 95% CI 0.46\u20130.90 in men, P-interaction = .91 for all-cause mortality at 42 months). Decline in 6-minute walk distance and quality-of-life scores was attenuated in both sexes, with no statistically detectable sex-specific interaction, and safety outcomes were comparable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Women with ATTR-CM demonstrated a distinct baseline phenotype in HELIOS-B. Despite this, vutrisiran showed no statistically detectable heterogeneity of treatment effect by sex within the limits of statistical power, supporting therapeutic benefit across the phenotypic spectrum of ATTR-CM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejhf\/xuag208","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T11:51:30Z","timestamp":1782388290000},"source":"Crossref","is-referenced-by-count":1,"title":["Consistent efficacy of vutrisiran across sexes in transthyretin cardiac amyloidosis: evidence from the HELIOS-B trial"],"prefix":"10.1093","author":[{"given":"Josephine","family":"Mansell","sequence":"first","affiliation":[{"name":"National Amyloidosis Centre, University College London , Royal Free Campus, Rowland Hill Street, London NW3 2PF ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karola S","family":"Jering","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Claggett","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira","family":"Zaroui","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Referral Center for Cardiac Amyloidosis, Filiere Cardiogen, GRC Amyloid Research Institute, APHP CHU Henri Mondor , Cr\u00e9teil 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Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arielle","family":"Abovich","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Gillmore","sequence":"additional","affiliation":[{"name":"National Amyloidosis Centre, University College London , Royal Free Campus, Rowland Hill Street, London NW3 2PF ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3698-9597","authenticated-orcid":false,"given":"Scott D","family":"Solomon","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, MA 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