DWI-FLAIR mismatch versus perfusion-based selection for extended window thrombolysis in acute ischemic stroke: a meta-analysis of randomized controlled trials

Abstract

To compare efficacy and safety outcomes of DWI–FLAIR mismatch versus CT/MR perfusion-based selection for intravenous thrombolysis (IVT) in extended-window acute ischemic stroke (AIS), we performed a systematic review and meta-analysis of randomized controlled trials enrolling adults with acute ischemic stroke treated with imaging-selected IVT beyond 4.5 h from last known well or with unknown onset. Trials using DWI–FLAIR mismatch or CT/MR perfusion selection were included. Outcomes were excellent functional outcome, functional independence, symptomatic intracranial hemorrhage (sICH), parenchymal hematoma, major bleeding, and mortality. Random-effects pairwise meta-analysis and Bucher-type indirect comparison were performed. Eight randomized trials including 2,546 patients were analyzed. Compared with best medical treatment, IVT improved excellent functional outcome (mRS 0–1: RR 1.27, 95% CI 1.14–1.40) and functional independence (mRS 0–2: RR 1.15, 95% CI 1.07–1.23), but increased sICH (RR 5.21, 95% CI 2.25–12.04). In imaging-stratified analyses, functional outcome RRs favored IVT in both perfusion-based and DWI–FLAIR mismatch-selected trials, with wider confidence intervals in the DWI–FLAIR subgroup. Hemorrhagic risk was increased with intravenous thrombolysis in both imaging subgroups, but subgroup interaction testing and a Bucher-type indirect comparison did not detect a statistically significant between-paradigm difference; the indirect comparison re-expresses the subgroup contrast rather than adding independent evidence. In AIS patients not planned for routine endovascular therapy, imaging-selected IVT beyond 4.5 h was associated with improved functional outcomes but increased sICH risk. No definitive superiority or equivalence was established between imaging strategies; imaging choice should be guided by clinical context, time window, EVT eligibility, local workflow, and patient-level factors. This meta-analysis included eight randomized controlled trials involving 2,546 patients and compared imaging-selected intravenous thrombolysis (IVT) with best medical treatment (BMT) beyond 4.5 hours from last known well or with unknown onset. Overall pairwise meta-analysis showed improved excellent functional outcome (mRS 0–1; RR 1.27, 95% CI 1.14–1.40) and functional independence (mRS 0–2; RR 1.15, 95% CI 1.07–1.23) with IVT, with an increased risk of symptomatic intracranial hemorrhage (RR 5.21, 95% CI 2.25–12.04). Imaging-stratified analyses showed treatment effects favoring IVT in both perfusion-based and DWI–FLAIR mismatch-selected trials. Subgroup interaction tests and the Bucher-type indirect comparison did not demonstrate a statistically significant difference between imaging-selection strategies. Abbreviations: IVT, intravenous thrombolysis; BMT, best medical treatment; DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery; mRS, modified Rankin Scale; RR, risk ratio; CI, confidence interval; sICH, symptomatic intracranial hemorrhage