Frailty as a Predictor of Clinical Outcomes After Acute Ischemic Stroke in Older Adults: A Systematic Review and...

Frailty, a state of reduced physiological reserve, is increasingly recognised as a determinant of outcome in older adults with acute ischaemic stroke (AIS) that is distinct from chronological age. We systematically reviewed and synthesised the association between pre-stroke/baseline frailty and clinical outcomes - mortality and poor functional outcome - after AIS in older adults, and examined effect modification by frailty instrument and by receipt of reperfusion therapy. We searched MEDLINE, Embase, Scopus, and Web of Science from inception to 20 June 2026 for original observational studies reporting an adjusted association between a defined frailty measure and mortality or functional outcome in older AIS patients, following PRISMA 2020. Two reviewers screened, extracted data, and appraised risk of bias with the Newcastle-Ottawa Scale. Maximally adjusted estimates were pooled with DerSimonian-Laird random-effects models, separately for odds ratios and hazard ratios and within homogeneous outcome/contrast groups; heterogeneity was quantified with I². Twelve studies met the eligibility criteria, five of which contributed a maximally adjusted estimate to meta-analysis. Across instruments (Clinical Frailty Scale, Hospital Frailty Risk Score, deficit-accumulation and laboratory frailty indices), higher frailty was consistently associated with increased mortality and worse functional outcome. In verified data, laboratory-index frailty (FI-LAB) independently predicted 12-month mortality after endovascular therapy (frail vs robust, adjusted HR 3.61, 95% CI 1.98-6.61), and each additional Hospital Frailty Risk Score point independently predicted 90-day mortality (adjusted OR 1.11, 95% CI 1.00-1.24) and worse functional outcome (adjusted OR 1.13, 95% CI 1.00-1.27). In random-effects meta-analyses restricted to cohorts reporting a maximally adjusted estimate, frailty was associated with more than doubled odds of poor functional outcome (pooled adjusted OR 2.44, 95% CI 1.11-5.35; I² = 53%; three cohorts) and with roughly tripled early mortality (pooled adjusted HR 3.24, 95% CI 1.67-6.27; I² = 0%; two cohorts), consistent in direction and magnitude with the most recent published synthesis (pooled OR 2.04 for poor functional outcome). Frailty is a robust, instrument-independent predictor of death and disability after AIS in older adults and merits routine assessment to inform prognosis and individualised care, rather than to justify withholding evidence-based treatment.