{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:49:16Z","timestamp":1783579756578,"version":"3.55.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Training Fellowship from The Vivensa Foundation","award":["JBGS22\\20"],"award-info":[{"award-number":["JBGS22\\20"]}]},{"name":"Stroke Association Senior Clinical Lectureship","award":["SA-SCL-MED-22\\100006"],"award-info":[{"award-number":["SA-SCL-MED-22\\100006"]}]},{"DOI":"10.13039\/501100000364","name":"Stroke Association","doi-asserted-by":"publisher","award":["PG2S21\\100018"],"award-info":[{"award-number":["PG2S21\\100018"]}],"id":[{"id":"10.13039\/501100000364","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018956","name":"NIHR Cambridge Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203312"],"award-info":[{"award-number":["NIHR203312"]}],"id":[{"id":"10.13039\/501100018956","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Frailty is common amongst individuals presenting with acute ischaemic stroke (AIS). Not only has frailty been found to have disease-modifying effects in terms of survival and disability after AIS, but it may also exert a treatment-modifying effect in reperfusion therapies. However, studies investigating this to date have frequently been of limited sample size, highlighting the potential for meta-analysis to definitively establish any treatment-modifying effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We investigate the effect of pre-stroke frailty on morbidity and mortality outcomes following reperfusion treatment (thrombectomy and thrombolysis) for AIS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic review was performed according to Preferred Reporting of Items in Systematic Reviews and Meta-Analyses guidelines, via searching the EMBASE, PubMed, Scopus and Web of Science databases up to August 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 11 relevant studies with 194,699 participants. Overall, the prevalence of frailty was 37.2% [frail (n\u2009=\u200972,311), non-frail (122,096)]. Frailty was associated with increased 90-day (RR 2.19 [95% CI 1.44\u20133.34]) and one-year mortality (RR 2.11 [95% CI 1.6\u20132.78]), but not with symptomatic intracranial haemorrhage (RR 1.23 [95% CI 0.78\u20131.96]) or modified Rankin score 3\u20135 (RR 2.20 [0.94\u20135.16]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Frailty has a consistent association with mortality at different time points after AIS reperfusion therapies. Despite some study heterogeneity, there is evidence that pre-stroke frailty is associated with increased mortality after treatment, though not with increased risks of symptomatic intracerebral haemorrhage or post-stroke disability. These findings suggest that routine pre-morbid frailty assessment may inform the decision-making process for AIS reperfusion treatment administration. This study highlights the need for large multi-centre prospective trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ageing\/afag080","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T12:46:56Z","timestamp":1773924416000},"source":"Crossref","is-referenced-by-count":1,"title":["Treatment-modifying effects of frailty on stroke reperfusion therapy outcomes: a systematic review and meta-analysis"],"prefix":"10.1093","volume":"55","author":[{"given":"Anakha","family":"Varma","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge, England ,","place":["United Kingdom of Great Britain and Northern Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv","family":"Bhakta","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge, England ,","place":["United Kingdom of Great Britain and Northern Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5385-2026","authenticated-orcid":false,"given":"Esmee","family":"Dohle","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge, England ,","place":["United Kingdom of Great Britain and Northern Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Warburton","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge, England ,","place":["United Kingdom of Great Britain and Northern Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7640-4701","authenticated-orcid":false,"given":"Nicholas R","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge, England ,","place":["United Kingdom of Great Britain and Northern Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"2026041219030080800_ref1","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1016\/S0140-6736(12)62167-9","article-title":"Frailty in elderly people","volume":"381","author":"Clegg","year":"2013","journal-title":"Lancet."},{"key":"2026041219030080800_ref2","doi-asserted-by":"publisher","DOI":"10.1186\/s12877-021-02684-y","article-title":"The dynamics of frailty development and progression in older adults in primary care in England (2006\u20132017): a retrospective cohort profile","volume":"22","author":"Fogg","year":"2022","journal-title":"BMC Geriatr"},{"key":"2026041219030080800_ref3","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1136\/jech-2023-221761","article-title":"Frailty index is an independent predictor of all-cause and cardiovascular mortality in Eastern Europe: a multicentre cohort study","volume":"79","author":"Court","year":"2024","journal-title":"J Epidemiol Community Health"},{"key":"2026041219030080800_ref4","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1093\/qjmed\/hcv066","article-title":"Association of the clinical frailty scale with hospital outcomes","volume":"108","author":"Wallis","year":"2015","journal-title":"Qjm."},{"key":"2026041219030080800_ref5","doi-asserted-by":"publisher","first-page":"855532","DOI":"10.3389\/fneur.2022.855532","article-title":"Association of pre-stroke frailty with prognosis of elderly patients with acute cerebral infarction: a cohort study","volume":"13","author":"Yang","year":"2022","journal-title":"Front Neurol"},{"key":"2026041219030080800_ref6","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afac064","article-title":"Prevalence and implications of frailty in acute stroke: systematic review & meta-analysis","volume":"51:","author":"Burton","year":"2022","journal-title":"Age Ageing"},{"key":"2026041219030080800_ref7","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1177\/17474930251345295","article-title":"Frailty and stroke: global implications for assessment, research, and clinical care-a WSO scientific statement","volume":"20","author":"Evans","year":"2025","journal-title":"Int J Stroke"},{"key":"2026041219030080800_ref8","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1503\/cmaj.150100","article-title":"Association between frailty and 30-day outcomes after discharge from hospital","volume":"187","author":"Kahlon","year":"2015","journal-title":"Cmaj."},{"key":"2026041219030080800_ref9","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1093\/ageing\/afaa004","article-title":"Clinical frailty independently predicts early mortality after ischaemic stroke","volume":"49","author":"Evans","year":"2020","journal-title":"Age Ageing"},{"key":"2026041219030080800_ref10","first-page":"1","article-title":"Frailty and early mortality following intracerebral hemorrhage","volume":"3","author":"Lewis","year":"2024","journal-title":"Cerebrovasc Dis"},{"key":"2026041219030080800_ref11","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1016\/S0140-6736(16)00163-X","article-title":"Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials","volume":"387","author":"Goyal","year":"2016","journal-title":"Lancet."},{"key":"2026041219030080800_ref12","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1056\/NEJMoa0804656","article-title":"Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke","volume":"359","author":"Hacke","year":"2008","journal-title":"N Engl J Med"},{"key":"2026041219030080800_ref13","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1177\/0269215519841417","article-title":"The prevalence of frailty among acute stroke patients, and evaluation of method of assessment","volume":"33","author":"Taylor-Rowan","year":"2019","journal-title":"Clin Rehabil"},{"key":"2026041219030080800_ref14","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1093\/ageing\/afz163","article-title":"The future incidence, prevalence and costs of stroke in the UK","volume":"49","author":"King","year":"2020","journal-title":"Age Ageing"},{"key":"2026041219030080800_ref15","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.2147\/CIA.S256070","article-title":"Cerebral thrombolysis in rural residents aged \u2265 80","volume":"Volume 15","author":"Sobolewski","year":"2020","journal-title":"Clin Interv Aging"},{"key":"2026041219030080800_ref16","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/S1474-4422(22)00044-8","article-title":"Research priorities to improve stroke outcomes","volume":"21","author":"Hill","year":"2022","journal-title":"Lancet Neurol"},{"key":"2026041219030080800_ref17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000545288","article-title":"Stroke medicine is frailty medicine: clinical and research priorities for frailty in stroke","volume":"15","author":"Evans","year":"2025","journal-title":"Cerebrovasc Dis"},{"key":"2026041219030080800_ref18","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.124.048424","article-title":"The importance of frailty in stroke and how to measure it","volume":"56","author":"Evans","year":"2024","journal-title":"Stroke."},{"key":"2026041219030080800_ref19","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"29","author":"Page","year":"2021","journal-title":"Bmj."},{"key":"2026041219030080800_ref20","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1186\/s13643-016-0384-4","article-title":"Rayyan-a web and mobile app for systematic reviews","volume":"5","author":"Ouzzani","year":"2016","journal-title":"Syst Rev"},{"key":"2026041219030080800_ref21","doi-asserted-by":"publisher","first-page":"108602","DOI":"10.1016\/j.envint.2024.108602","article-title":"A tool to assess risk of bias in non-randomized follow-up studies of exposure effects (ROBINS-E)","volume":"186","author":"Higgins","year":"2024","journal-title":"Environ Int"},{"key":"2026041219030080800_ref22","doi-asserted-by":"publisher","first-page":"261","DOI":"10.3102\/10769986030003261","article-title":"Bias and efficiency of meta-analytic variance estimators in the random-effects model","volume":"30","author":"Viechtbauer","year":"2005","journal-title":"Journal of Educational and Behavioral Statistics"},{"key":"2026041219030080800_ref23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v036.i03","article-title":"Conducting meta-analyses in R with the metafor package","volume":"36","author":"Viechtbauer","year":"2010","journal-title":"J Stat Softw"},{"key":"2026041219030080800_ref24","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afac096","article-title":"Effect of frailty on outcomes of endovascular treatment for acute ischaemic stroke in older patients","volume":"51","author":"Tan","year":"2022","journal-title":"Age Ageing"},{"key":"2026041219030080800_ref25","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afab260","article-title":"Frailty and stroke thrombectomy outcomes-an observational cohort study","volume":"51","author":"Joyce","year":"2022","journal-title":"Age Ageing"},{"key":"2026041219030080800_ref26","doi-asserted-by":"publisher","first-page":"106816","DOI":"10.1016\/j.jstrokecerebrovasdis.2022.106816","article-title":"Clinical frailty and outcome after mechanical thrombectomy for stroke in patients aged \u2265 80 years","volume":"31","author":"Tiainen","year":"2022","journal-title":"J Stroke Cerebrovasc Dis"},{"key":"2026041219030080800_ref27","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.3390\/jcm10102171","article-title":"Analysis of frailty in geriatric patients as a prognostic factor in endovascular treated patients with large vessel occlusion strokes","volume":"10","author":"Schnieder","year":"2021","journal-title":"J Clin Med"},{"key":"2026041219030080800_ref28","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1177\/23969873251344202","article-title":"Frailty's influence on older stroke patients: neurological outcome and mortality after endovascular treatment in stroke: a national German stroke registry analysis","volume":"10","author":"Schnieder","year":"2025","journal-title":"Eur Stroke J"},{"key":"2026041219030080800_ref29","doi-asserted-by":"publisher","first-page":"15910199251342854","DOI":"10.1177\/15910199251342854","article-title":"National assessment of frailty impact on endovascular mechanical thrombectomy for minor to moderately severe large vessel occlusions per NIHSS","volume":"2","author":"Gajjar","year":"2025","journal-title":"Interv Neuroradiol"},{"key":"2026041219030080800_ref30","doi-asserted-by":"publisher","first-page":"523","DOI":"10.2147\/CIA.S504456","article-title":"Association between premorbid frailty status and functional independence in acute ischemic stroke patients following endovascular treatment in the late window","volume":"20","author":"Huang","year":"2025","journal-title":"Clin Interv Aging"},{"key":"2026041219030080800_ref31","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1007\/s00234-025-03562-9","article-title":"Association of frailty with outcomes in patients with large vessel occlusion stroke undergoing mechanical thrombectomy","volume":"67","author":"Bahar","year":"2025","journal-title":"Neuroradiology."},{"key":"2026041219030080800_ref32","doi-asserted-by":"publisher","first-page":"3338","DOI":"10.1007\/s00415-022-10966-7","article-title":"Premorbid frailty predicts short- and long-term outcomes of reperfusion treatment in acute stroke","volume":"269","author":"Pilotto","year":"2022","journal-title":"J Neurol"},{"key":"2026041219030080800_ref33","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1016\/j.bbi.2011.02.008","article-title":"Brain inflammation is induced by co-morbidities and risk factors for stroke","volume":"25","author":"Drake","year":"2011","journal-title":"Brain Behav Immun"},{"key":"2026041219030080800_ref34","doi-asserted-by":"publisher","first-page":"2021","DOI":"10.3389\/fneur.2021.690935","article-title":"Carotid Atheroinflammation is associated with cerebral small vessel disease severity","volume":"12","author":"Evans","year":"2021","journal-title":"Frontiers in Neurology [Original Research]"},{"key":"2026041219030080800_ref35","doi-asserted-by":"publisher","first-page":"e439","DOI":"10.1212\/WNL.0000000000008881","article-title":"Imaging markers of small vessel disease and brain frailty, and outcomes in acute stroke","volume":"94","author":"Appleton","year":"2020","journal-title":"Neurology."},{"key":"2026041219030080800_ref36","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1159\/000546563","article-title":"Carotid atherosclerosis shows distinct patterns of Atheroinflammation and microcalcification relating to frailty and multimorbidity","volume":"55","author":"Evans","year":"2025","journal-title":"Cerebrovasc Dis"},{"key":"2026041219030080800_ref37","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afae266","article-title":"Frailty reduces penumbral volumes and attenuates treatment response in hyperacute ischemic stroke","volume":"53","author":"Dohle","year":"2024","journal-title":"Age Ageing"},{"key":"2026041219030080800_ref38","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afad248","article-title":"Constructing a quality frailty index: you get out what you put in","volume":"53","author":"Hanlon","year":"2024","journal-title":"Age Ageing"}],"container-title":["Age and Ageing"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ageing\/article-pdf\/55\/4\/afag080\/68024060\/afag080.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ageing\/article-pdf\/55\/4\/afag080\/68024060\/afag080.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T23:35:44Z","timestamp":1776036944000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ageing\/article\/doi\/10.1093\/ageing\/afag080\/8651038"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":38,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4,4]]}},"URL":"https:\/\/doi.org\/10.1093\/ageing\/afag080","relation":{},"ISSN":["0002-0729","1468-2834"],"issn-type":[{"value":"0002-0729","type":"print"},{"value":"1468-2834","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2026,4]]},"article-number":"afag080"}}