Adjunctive intra-arterial thrombolysis following successful endovascular thrombectomy for acute ischemic stroke: a systematic review and meta-analysis of 8 randomized controlled trials

Abstract

Background: Endovascular thrombectomy (EVT) is the treatment of choice for acute ischemic stroke (AIS) caused by large vessel occlusion, substantially improving recanalization rates and clinical outcomes. However, despite successful reperfusion, less than half of patients remain disability-free at 90 days, highlighting the persistent gap between angiographic success and functional recovery. This residual disability may result not only from irreversible ischemic injury occurring before reperfusion, but also from potentially reversible mechanisms, including persistent or newly formed distal thrombi and microcirculatory obstruction. Intra-arterial thrombolysis (IAT) administered after EVT has emerged as a potential adjunctive strategy to enhance tissue-level reperfusion, yet its efficacy and safety compared with standard medical treatment remain uncertain. Objective: To evaluate the effectiveness and safety of adjunctive IAT versus standard medical treatment (SMT) in patients with AIS who achieved successful reperfusion after EVT. Methods: This systematic review and meta-analysis was performed in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA guidelines. A systematic search of PubMed, Embase, and the Cochrane Library was conducted from database inception to January 2026. We included randomized controlled trials (RCTs) enrolling patients with AIS who achieved successful reperfusion after EVT that compared IAT with SMT and reported at least one prespecified outcome. The efficacy outcomes were modified Rankin Scale (mRS) 0-1 and mRS 0-2. Included safety outcomes were any intracranial hemorrhage (aICH), symptomatic intracranial hemorrhage (sICH) and mortality. Pooled risk ratios (RRs) with corresponding 95% confidence intervals (CIs) were estimated using a random-effects Mantel–Haenszel model. Results: Eight RCTs including 2,561 patients (1,296 IAT and 1,265 SMT) were analyzed. Adjunctive IAT was associated with a higher relative risk of achieving mRS 0–1 at 90 days (RR 1.25, 95% CI: 1.12–1.38; p<0.001; I²=10.5%). No significant difference was observed for mRS 0–2 (RR 1.04, 95% CI: 0.97–1.11; p=0.256; I²=0%). Regarding safety outcomes, IAT was associated with a borderline increase in aICH (RR 1.15, 95% CI: 1.00–1.33; p=0.045; I²=2.1%), whereas no significant difference was found in sICH (RR 1.17, 95% CI: 0.79–1.72; p=0.439; I²=0%) and mortality rates (RR 1.04, 95% CI: 0.87–1.23; p=0.691; I²=22.9%). Overall heterogeneity was low across analyses. Conclusion: In patients with AIS who achieved successful reperfusion after EVT, adjunctive IAT was associated with improved rates of excellent functional outcome (mRS 0–1), without an increase in sICH or mortality, although a modest rise in overall aICH was observed. These findings suggest a potential functional benefit of IAT at the expense of a slight increase in radiographic hemorrhagic events, warranting confirmation in more adequately powered RCTs.