Key result
Adjunctive intra-arterial thrombolysis with EVT yields ~40% higher rates of excellent 90-day functional recovery.
Why the study?
Nearly half of patients with AIS-LVO who achieve successful reperfusion with EVT do not reach functional independence. Adjunctive intra-arterial thrombolysis targets residual distal thrombi and microcirculatory impairment, but the efficacy and safety of different thrombolytics remain uncertain.
Does adjunctive intra-arterial thrombolysis (alteplase, tenecteplase, or urokinase) combined with endovascular thrombectomy improve 90-day functional outcomes compared to endovascular thrombectomy alone in patients with acute ischemic stroke due to large vessel occlusion?
Meta-Analysis (n=2,564)
Open-label with blinded endpoint assessment in most trials (1 double-blind trial)
Randomized controlled trials included
Yes
Does adjunctive intra-arterial thrombolysis (alteplase, tenecteplase, or urokinase) combined with endovascular thrombectomy improve 90-day functional outcomes compared to endovascular thrombectomy alone in patients with acute ischemic stroke due to large vessel occlusion?
In patients with acute large-vessel occlusion stroke undergoing endovascular thrombectomy, adjunctive intra-arterial alteplase or tenecteplase significantly improves 90-day excellent clinical outcomes (mRS 0-1) without a statistically significant increase in symptomatic intracranial hemorrhage.
Answers are grounded in this paper and cite their sources.
Adjunctive IA alteplase or tenecteplase improves excellent 90-day outcomes after EVT; extends RCT evidence for combination therapy in large-vessel occlusion.
Background While endovascular thrombectomy (EVT) is standard care for acute ischemic stroke due to large vessel occlusion (AIS-LVO), but nearly half of patients with successful reperfusion do not achieve functional independence. Adjunctive intra-arterial thrombolysis (IAT) aims to address residual distal thrombi and microcirculatory impairment; however, the efficacy and safety of IAT in comparison with other thrombolytics remain uncertain. Methods We conducted a network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing EVT alone vs. EVT combined with IAT using alteplase (ALT), tenecteplase (TNK), or urokinase (UK) in AIS-LVO patients. Primary outcomes were excellent clinical outcome (mRS 0–1) and functional independence (mRS 0–2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and all-cause mortality. Results Eight RCTs involving 2,564 patients were included. For excellent clinical (mRS 0–1), EVT + IA-ALT ranked highest [surface under the cumulative ranking curve (SUCRA) 96.2%], followed by EVT + IA-TNK (59.8%). Both showed significant benefits over EVT alone [EVT + IA-TNK vs. EVT: RR 1.20, 95% CI 1.05–1.39. EVT + IA-ALT vs. EVT: RR 1.40, 95% CI 1.21–1.63 and EVT + IA-TNK (0.125 mg/kg) vs. EVT: RR 1.54, 95% CI 1.07–2.20. EVT + IA-ALT (0.225 mg/kg) vs. EVT: RR 1.40, 95% CI 1.21–1.63]. For functional independence (mRS 0–2), EVT + IA-ALT also ranked highest, but no combination strategy showed a statistically significant benefit over EVT alone in pairwise comparisons. Regarding safety, point estimates for sICH risk did not differ significantly between combination strategies and EVT alone. However, EVT + IA-TNK demonstrated a statistically significant advantage over EVT + IA-ALT in terms of lower all-cause mortality (RR 1.58, 95% CI 1.01–2.46). Conclusions EVT + IA-ALT and EVT + IA-TNK may improve excellent clinical outcome without a statistically significant increase in sICH; however, clinically important bleeding risk cannot be excluded. In exploratory indirect comparisons, EVT + IA-TNK was associated with lower all-cause mortality than EVT + IA-ALT, although this finding is based on sparse evidence and should be interpreted with caution. Systematic Review Registration PROSPERO CRD420261465567.
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Ma et al. (2026) conducted a meta-analysis in Acute ischemic stroke due to large vessel occlusion (AIS-LVO) (n=2,564). Adjunctive intra-arterial thrombolysis (Alteplase, Tenecteplase, or Urokinase) with endovascular thrombectomy vs. Endovascular thrombectomy (EVT) alone or with placebo was evaluated on Excellent clinical outcome (modified Rankin Scale [mRS] 0–1) at 90 days (EVT + IA-Alteplase vs. EVT alone) (RR 1.40, 95% CI 1.21-1.63). Adjunctive intra-arterial alteplase (RR 1.40, 95% CI 1.21–1.63) and tenecteplase (RR 1.20, 95% CI 1.05–1.39) with EVT significantly increased 90-day mRS 0–1 vs EVT alone.
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