{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T20:06:20Z","timestamp":1779912380077,"version":"3.53.1"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Evidence on antiarrhythmic drugs (AADs) in the oldest atrial fibrillation (AF) patients is limited. We investigated clinical characteristics and outcomes associated with AADs use in this population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The oldest (age\u2009\u2265\u200980\u00a0years) AF patients from the nationwide START registry were included. Patients were divided into three groups: no AADs (n\u2009=\u20093573), class 1c-AADs (n\u2009=\u2009207) and Amiodarone (n\u2009=\u2009464). Factors associated with AADs were evaluated using multivariable logistic regression models. The associations between AADs and all-cause mortality were assessed using Cox proportional hazards models and cardiovascular events (CVEs) were analysed using Fine-Gray competing risk models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 4244 patients (54.9% women), the mean age was 84.8\u2009\u00b1\u20093.8\u00a0years. AADs were prescribed in 671 patients (15.8%), including amiodarone in 464 (10.9%) and 1c-AADs in 207 (4.9%). 1c-AADs use was associated with younger age and fewer comorbidities, including lower prevalence of diabetes, heart failure, chronic obstructive pulmonary disease\/obstructive sleep apnoea and better functional and social status. Amiodarone use was associated with coronary artery disease and markers of frailty. Over a median follow-up of 502 (interquartile range 362\u2013857) days, 492 deaths and 548 CVEs occurred. In unadjusted analyses, 1c-AADs were associated with lower all-cause mortality and CVEs; however, these associations were no longer significant after multivariable adjustment. Amiodarone use was not associated with clinical outcomes in either unadjusted or adjusted analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In the oldest AF patients, AADs use is influenced by comorbidity burden and frailty-related characteristics. AADs were not independently associated with mortality or CVEs, suggesting that pharmacological rhythm control may be reserved for selected cases in this population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ageing\/afag157","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T11:41:10Z","timestamp":1778586070000},"source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological rhythm control strategy and outcomes in the oldest atrial fibrillation patients: an analysis of the nationwide Italian START registry"],"prefix":"10.1093","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9467-5903","authenticated-orcid":false,"given":"Danilo","family":"Menichelli","sequence":"first","affiliation":[{"name":"Department of General Surgery, Surgical Specialty and Anesthesiology, University of Rome La Sapienza , Rome, Lazio ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Gazzaniga","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Surgical Specialty and Anesthesiology, University of Rome La Sapienza , Rome, Lazio ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Poli","sequence":"additional","affiliation":[{"name":"Center of Atherothrombotic Disease, University Hospital Careggi , Florence, Tuscany ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giordano","family":"Di Carlo","sequence":"additional","affiliation":[{"name":"Postgraduate School of Internal Medicine, Department of Internal Medicine and Medical Specialties, University of Rome La Sapienza , Rome, Lazio ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Antonucci","sequence":"additional","affiliation":[{"name":"Arianna Anticoagulation Foundation , Bologna, Emilia-Romagna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Violi","sequence":"additional","affiliation":[{"name":"Department of Medical and Cardiovascular Sciences, University of Rome La Sapienza , Rome, Lazio ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2265-7455","authenticated-orcid":false,"given":"Pasquale","family":"Pignatelli","sequence":"additional","affiliation":[{"name":"Department of Medical and Cardiovascular Sciences, University of Rome La Sapienza , Rome, Lazio ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6357-5213","authenticated-orcid":false,"given":"Daniele","family":"Pastori","sequence":"additional","affiliation":[{"name":"Department of Medical and Cardiovascular Sciences, University of Rome La Sapienza , Rome, Lazio ,","place":["Italy"]},{"name":"IRCCS Istituto Neurologico Mediterraneo NEUROMED , Pozzilli, Molise ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"2026052715433655800_ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacadv.2024.101117","article-title":"Incidence of all-cause, cardiovascular, and atrial fibrillation-related hospitalizations: focus on antiarrhythmic drugs","volume":"3","author":"Menichelli","year":"2024","journal-title":"JACC Adv"},{"key":"2026052715433655800_ref2","doi-asserted-by":"publisher","first-page":"e077209","DOI":"10.1136\/bmj-2023-077209","article-title":"Temporal trends in lifetime risks of atrial fibrillation and its complications between 2000 and 2022: Danish, nationwide, population based cohort study","volume":"385","author":"Vinter","year":"2024","journal-title":"BMJ"},{"key":"2026052715433655800_ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2023.100801","article-title":"Atrial fibrillation: better symptom control with rate and rhythm management","volume":"37","author":"Gupta","year":"2024","journal-title":"Lancet Reg Health Eur"},{"key":"2026052715433655800_ref4","doi-asserted-by":"publisher","first-page":"3314","DOI":"10.1093\/eurheartj\/ehae176","article-title":"2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS)","volume":"45","author":"Van Gelder","year":"2024","journal-title":"Eur Heart J"},{"key":"2026052715433655800_ref5","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1016\/j.mayocp.2018.10.022","article-title":"Integrated Care Management of Patients with atrial fibrillation and risk of cardiovascular events: the ABC (atrial fibrillation better care) pathway in the ATHERO-AF study cohort","volume":"94","author":"Pastori","year":"2019","journal-title":"Mayo Clin Proc"},{"key":"2026052715433655800_ref6","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1016\/j.jacep.2024.03.006","article-title":"Rhythm vs rate control strategy for atrial fibrillation: a meta-analysis of randomized controlled trials","volume":"10","author":"Zafeiropoulos","year":"2024","journal-title":"JACC Clin Electrophysiol"},{"key":"2026052715433655800_ref7","doi-asserted-by":"publisher","first-page":"617","DOI":"10.2165\/11591680-000000000-00000","article-title":"Is antiarrhythmic treatment in the elderly different? A review of the specific changes","volume":"28","author":"Deneer","year":"2011","journal-title":"Drugs Aging"},{"key":"2026052715433655800_ref8","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1111\/j.1076-7460.2002.0069.x","article-title":"Special problems with antiarrhythmic drugs in the elderly: safety, tolerability, and efficacy","volume":"11","author":"Dayer","year":"2002","journal-title":"Am J Geriatr Cardiol"},{"key":"2026052715433655800_ref9","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1111\/j.1532-5415.1992.tb01957.x","article-title":"Effects of advancing age on the efficacy and side effects of antiarrhythmic drugs in post-myocardial infarction patients with ventricular arrhythmias. The CAST investigators","volume":"40","author":"Akiyama","year":"1992","journal-title":"J Am Geriatr Soc"},{"key":"2026052715433655800_ref10","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1080\/14779072.2025.2561717","article-title":"Reviewing the use of antiarrhythmic drugs in elderly patients with atrial fibrillation","volume":"23","author":"Menichelli","year":"2025","journal-title":"Expert Rev Cardiovasc Ther"},{"key":"2026052715433655800_ref11","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1186\/s12872-021-01951-5","article-title":"Incidence and predictors of hospitalization in patients with atrial fibrillation: results from the Chinese atrial fibrillation registry study","volume":"21","author":"Dong","year":"2021","journal-title":"BMC Cardiovasc Disord"},{"key":"2026052715433655800_ref12","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/j.ahj.2014.02.003","article-title":"Drivers of hospitalization for patients with atrial fibrillation: results from the outcomes registry for better informed treatment of atrial fibrillation (ORBIT-AF)","volume":"167","author":"Steinberg","year":"2014","journal-title":"Am Heart J"},{"key":"2026052715433655800_ref13","doi-asserted-by":"publisher","first-page":"e026410","DOI":"10.1161\/JAHA.122.026410","article-title":"Incidence and risk factors for residual adverse events despite anticoagulation in atrial fibrillation: results from phase II\/III of the GLORIA-AF registry","volume":"11","author":"Ding","year":"2022","journal-title":"J Am Heart Assoc"},{"key":"2026052715433655800_ref14","doi-asserted-by":"publisher","first-page":"1700921","DOI":"10.3389\/fcvm.2025.1700921","article-title":"Outcomes of early rhythm control vs. rate control strategies for atrial fibrillation in late elderly patients: a systematic review and meta-analysis","volume":"12","author":"Ahmad","year":"2025","journal-title":"Front Cardiovasc Med"},{"key":"2026052715433655800_ref15","doi-asserted-by":"publisher","first-page":"e14321","DOI":"10.1111\/eci.14321","article-title":"Long-term cognitive function changes with non-vitamin K oral anticoagulants in older patients with atrial fibrillation. A multicenter cohort study","volume":"55","author":"Armentaro","year":"2025","journal-title":"Eur J Clin Invest"},{"key":"2026052715433655800_ref16","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.ejim.2023.08.019","article-title":"Renin-angiotensin-aldosterone system inhibitors and mortality risk in elderly patients with atrial fibrillation. Insights from the nationwide START registry","volume":"119","author":"Menichelli","year":"2024","journal-title":"Eur J Intern Med"},{"key":"2026052715433655800_ref17","doi-asserted-by":"publisher","first-page":"3538","DOI":"10.1093\/eurheartj\/ehae179","article-title":"2024 ESC Guidelines for the management of peripheral arterial and aortic diseases","volume":"45","author":"Mazzolai","year":"2024","journal-title":"Eur Heart J"},{"key":"2026052715433655800_ref18","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.ejim.2024.03.014","article-title":"Sex-based differences in the comprehensive geriatric assessment in elderly hospitalized patients with non-valvular atrial fibrillation","volume":"125","author":"Armentaro","year":"2024","journal-title":"Eur J Intern Med"},{"key":"2026052715433655800_ref19","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.005401","article-title":"Prospective assessment of sex-related differences in symptom status and health perception among patients with atrial fibrillation","volume":"6","author":"Blum","year":"2017","journal-title":"J Am Heart Assoc"},{"key":"2026052715433655800_ref20","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1093\/europace\/euy295","article-title":"Sex differences in rate and rhythm control for atrial fibrillation","volume":"21","author":"Weberndorfer","year":"2019","journal-title":"EP Europace"},{"key":"2026052715433655800_ref21","doi-asserted-by":"publisher","first-page":"e007955","DOI":"10.1161\/CIRCEP.121.007955","article-title":"Drug interactions affecting antiarrhythmic drug use","volume":"15","author":"Mar","year":"2022","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"2026052715433655800_ref22","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.acvd.2013.04.001","article-title":"Expert consensus of the French Society of Geriatrics and Gerontology and the French Society of Cardiology on the management of atrial fibrillation in elderly people","volume":"106","author":"Hanon","year":"2013","journal-title":"Arch Cardiovasc Dis"},{"key":"2026052715433655800_ref23","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-025-01936-8","article-title":"Frailty elements, direct oral anticoagulants and mortality risk in atrial fibrillation patients aged &gt;\/= 80 or &gt;\/= 90 years from the nationwide Italian START registry: a propensity score matching analysis","author":"Menichelli","year":"2025","journal-title":"Geroscience"},{"key":"2026052715433655800_ref24","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1001\/archinternmed.2012.2266","article-title":"Comparative effectiveness of rhythm control vs rate control drug treatment effect on mortality in patients with atrial fibrillation","volume":"172","author":"Ionescu-Ittu","year":"2012","journal-title":"Arch Intern Med"},{"key":"2026052715433655800_ref25","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.ahj.2004.09.038","article-title":"Clinical factors that influence response to treatment strategies in atrial fibrillation: the atrial fibrillation follow-up investigation of rhythm management (AFFIRM) study","volume":"149","author":"Curtis","year":"2005","journal-title":"Am Heart J"},{"key":"2026052715433655800_ref26","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1056\/NEJMoa021328","article-title":"A comparison of rate control and rhythm control in patients with atrial fibrillation","volume":"347","author":"Wyse","year":"2002","journal-title":"N Engl J Med"}],"container-title":["Age and Ageing"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ageing\/article-pdf\/55\/5\/afag157\/68412873\/afag157.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ageing\/article-pdf\/55\/5\/afag157\/68412873\/afag157.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:43:42Z","timestamp":1779911022000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ageing\/article\/doi\/10.1093\/ageing\/afag157\/8696332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":26,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5,3]]}},"URL":"https:\/\/doi.org\/10.1093\/ageing\/afag157","relation":{},"ISSN":["0002-0729","1468-2834"],"issn-type":[{"value":"0002-0729","type":"print"},{"value":"1468-2834","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,5]]},"published":{"date-parts":[[2026,5]]},"article-number":"afag157"}}