Treatment-modifying Effects of Frailty on Stroke Reperfusion Therapy Outcomes: A Systematic Review and Meta-analysis

Background: 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. Objectives: We investigate the effect of pre-stroke frailty on morbidity and mortality outcomes following reperfusion treatment (thrombectomy and thrombolysis) for AIS. Methods: A systematic review was performed according to PRISMA guidelines, via searching the EMBASE, PubMed, Scopus, and Web of Science databases up to August 2025. Results: We identified 11 relevant studies with 194,699 participants. Overall, the prevalence of frailty was 37.2% [frail (n=72,311), non-frail (122,096)]. Frailty was associated with increased 90-day (RR 2.19 [95% CI 1.44-3.34]) and one-year mortality (RR 2.11 [95% CI 1.6-2.78]), but not with symptomatic intracranial haemorrhage (RR 1.23 [95% CI 0.78-1.96]) or modified Rankin score 3-5 (RR 2.20 [0.94-5.16]). Conclusions: 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.