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 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.

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.