{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:11:44Z","timestamp":1789186304193,"version":"build-2803163510"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":71,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Transthyretin amyloid cardiomyopathy (ATTR-CM) predominantly affects older adults, and tafamidis has proven efficacy in reducing mortality and hospitalizations in this population. However, its clinical benefit in octogenarians remains uncertain due to limited life expectancy, frailty, and other age-related factors. This meta-analysis evaluates the effect of tafamidis in patients aged\u2009\u2265\u200980 years, aiming to address the gap in evidence regarding the therapy\u2019s impact in this population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic review and meta-analysis were conducted by searching PubMed, Embase, and Cochrane databases for studies comparing tafamidis versus control in patients aged\u2009\u2265\u200980 years with transthyretin amyloidosis. The primary outcome was all-cause mortality. Hazard ratios (HRs) were pooled using a random-effects model, and heterogeneity was assessed using I\u00b2 statistics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three studies with a total of 1,866 participants were included (1 randomized controlled trial, 1 prospective cohort, and 1 retrospective study). The majority (77.3%) of patients received tafamidis, and the mean age was 84 years. Tafamidis was associated with a significant reduction in all-cause mortality (HR: 0.51; 95% CI 0.40\u20130.67;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01; I\u00b2 = 10.3%). Sensitivity analyses confirmed the robustness of this finding. The tafamidis group showed no increased risk of adverse events compared to controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Tafamidis significantly reduces all-cause mortality in octogenarian patients with ATTR-CM, supporting its use as a cornerstone therapy in this population. Further randomized controlled trials are needed to validate these findings and optimize treatment strategies in very elderly patients with advanced disease or comorbidities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-026-04422-2","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T10:06:37Z","timestamp":1780999597000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mortality in octogenarian patients with transthyretin amyloidosis treated with tafamidis: a systematic review and meta-analysis"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9136-1280","authenticated-orcid":false,"given":"Christiane","family":"Santo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius Machado","family":"Correia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria L. R.","family":"Defante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Ferlin Saccomani","family":"Barbosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Dabarian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Vaz Kerges","family":"Bueno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vagner Madrini","family":"Junior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"4422_CR1","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.ijcard.2018.06.006","volume":"270","author":"L Mohamed-Salem","year":"2018","unstructured":"Mohamed-Salem L, Santos-Mateo JJ, Sanchez-Serna J, Hern\u00e1ndez-Vicente \u00c1, Reyes-Marle R, Castell\u00f3n S\u00e1nchez MI, et al. Prevalence of wild type ATTR assessed as myocardial uptake in bone scan in the elderly population. Int J Cardiol. 2018;270:192\u20136.","journal-title":"Int J Cardiol"},{"issue":"3","key":"4422_CR2","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1080\/07853890701842988","volume":"40","author":"M Tanskanen","year":"2008","unstructured":"Tanskanen M, Peuralinna T, Polvikoski T, Notkola IL, Sulkava R, Hardy J, et al. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: A population-based autopsy study. Ann Med. 2008;40(3):232\u20139.","journal-title":"Ann Med"},{"key":"4422_CR3","doi-asserted-by":"crossref","unstructured":"Muchtar E, Dispenzieri A, Magen H, Grogan M, Mauermann M, McPhail ED, et al. Systemic amyloidosis from A (AA) to T (ATTR): a review. J Intern Med. 2021;289:268\u201392.","DOI":"10.1111\/joim.13169"},{"key":"4422_CR4","volume-title":"Cardiac Amyloidosis in Older Adults With a Focus on Frailty: JACC: Advances Expert Consensus","author":"NK Bart","year":"2025","unstructured":"Bart NK, Bianchi G, Cuddy SAM, Goyal P, Griffin JM, Hummel SL, et al. Cardiac Amyloidosis in Older Adults With a Focus on Frailty: JACC: Advances Expert Consensus. Volume 4. JACC: Advances. Elsevier B.V.; 2025."},{"issue":"11","key":"4422_CR5","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1056\/NEJMoa1805689","volume":"379","author":"MS Maurer","year":"2018","unstructured":"Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, et al. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018;379(11):1007\u201316.","journal-title":"N Engl J Med"},{"key":"4422_CR6","doi-asserted-by":"crossref","unstructured":"Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372.","DOI":"10.1136\/bmj.n71"},{"key":"4422_CR7","unstructured":"Higgins JPTTJCJCMLTPM, et al. editors. Cochrane Handbook for Systematic Reviews of Interventions version 6.5 (updated August 2024). Cochrane. 2024."},{"key":"4422_CR8","doi-asserted-by":"crossref","unstructured":"McGuinness LA, Higgins JPT. Risk-of-bias VISualization (robvis): an R package and shiny web app for visualizing risk-of-bias assessments. In Research Synthesis Methods. John Wiley and Sons Ltd; 2021:55\u201361.","DOI":"10.1002\/jrsm.1411"},{"issue":"5","key":"4422_CR9","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1177\/1060028019888489","volume":"54","author":"J Park","year":"2020","unstructured":"Park J, Egolum U, Parker S, Andrews E, Ombengi D, Ling H. Tafamidis: A First-in-Class Transthyretin Stabilizer for Transthyretin Amyloid Cardiomyopathy. Ann Pharmacother. 2020;54(5):470\u20137.","journal-title":"Ann Pharmacother"},{"key":"4422_CR10","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.amjcard.2021.02.035","volume":"148","author":"AB Miller","year":"2021","unstructured":"Miller AB, Januzzi JL, O\u2019Neill BJ, Gundapaneni B, Patterson TA, Sultan MB, et al. Causes of Cardiovascular Hospitalization and Death in Patients With Transthyretin Amyloid Cardiomyopathy (from the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial [ATTR-ACT]). Am J Cardiol. 2021;148:146\u201350.","journal-title":"Am J Cardiol"},{"key":"4422_CR11","doi-asserted-by":"crossref","unstructured":"Ruberg FL, Maurer MS. Cardiac amyloidosis due to transthyretin protein. JAMA. 2024;331:778\u201391.","DOI":"10.1001\/jama.2024.0442"},{"issue":"11","key":"4422_CR12","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1093\/eurheartj\/ehae923","volume":"46","author":"P Debonnaire","year":"2025","unstructured":"Debonnaire P, Dujardin K, Verheyen N, Pouleur AC, Droogmans S, Claeys M, et al. Tafamidis in octogenarians with wild-type transthyretin cardiac amyloidosis: an international cohort study. Eur Heart J. 2025;46(11):1057\u201370.","journal-title":"Eur Heart J"},{"key":"4422_CR13","doi-asserted-by":"crossref","unstructured":"Jobb\u00e9-Duval A, Kharoubi M, Donal E, Bauer F, Broussier A, Bisson A, et al. Impact of tafamidis on survival in elderly patients: insights from the healthcare European Amyloidosis Registry. Int J Cardiol. 2025;437.","DOI":"10.1016\/j.ijcard.2025.133522"},{"issue":"1","key":"4422_CR14","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.jchf.2023.08.032","volume":"12","author":"P Garcia-Pavia","year":"2024","unstructured":"Garcia-Pavia P, Sultan MB, Gundapaneni B, Sekijima Y, Perfetto F, Hanna M, et al. Tafamidis Efficacy Among Octogenarian Patients in the Phase 3 ATTR-ACT and Ongoing Long-Term Extension Study. JACC Heart Fail. 2024;12(1):150\u201360.","journal-title":"JACC Heart Fail"},{"key":"4422_CR15","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3390\/jcm13175291","volume":"13","author":"S Dobner","year":"2024","unstructured":"Dobner S, Zarro S, Wieser F, Kassar M, Alaour B, Wiedemann S, et al. Effect of Timely Availability of TTR-Stabilizing Therapy on Diagnosis, Therapy, and Clinical Outcomes in ATTR-CM. J Clin Med. 2024;13:17.","journal-title":"J Clin Med"},{"issue":"1","key":"4422_CR16","doi-asserted-by":"publisher","first-page":"E7","DOI":"10.1161\/CIR.0000000000000792","volume":"142","author":"MM Kittleson","year":"2020","unstructured":"Kittleson MM, Maurer MS, Ambardekar AV, Bullock-Palmer RP, Chang PP, Eisen HJ, et al. Cardiac Amyloidosis: Evolving Diagnosis and Management: A Scientific Statement From the American Heart Association. Circulation. 2020;142(1):E7\u201322.","journal-title":"Circulation"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-026-04422-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-026-04422-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-026-04422-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T22:23:20Z","timestamp":1787091800000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13023-026-04422-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":16,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4422"],"URL":"https:\/\/doi.org\/10.1186\/s13023-026-04422-2","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,9]]},"assertion":[{"value":"15 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"As this meta-analysis utilized only data from previously published studies, it did not involve direct interaction with human or animal subjects. Consequently, formal ethical approval was not required. The original studies included in this analysis adhered to the ethical guidelines of their respective institutions and the principles outlined in the Declaration of Helsinki.","order":1,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"CRD420251146576","order":3,"name":"Ethics","label":"Prospective register of systematic reviews (PROSPERO)","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"282"}}