Adjunctive intra-arterial thrombolysis after endovascular thrombectomy in acute ischaemic stroke: a systematic review and network meta-analysis

Background Endovascular thrombectomy is the standard treatment for acute ischaemic stroke (AIS) due to large vessel occlusion (LVO). However, fewer than half of patients achieve functional independence despite successful thrombectomy. Previous meta-analysis showed adjunctive intra-arterial thrombolysis (IAT) may improve outcomes but whether efficacy and safety differ among thrombolytic agents remains unclear.Objective To compare IAT agents—tenecteplase (TNK), alteplase and urokinase—post-thrombectomy for AIS due to LVO.Methods Randomised controlled trials (RCTs) evaluating IAT after successful recanalisation were included. Excellent functional outcome at 90 days (modified Rankin Scale (mRS) 0–1) was the primary outcome. Secondary outcomes were mRS 0–2, symptomatic intracranial haemorrhage (sICH) and all-cause mortality at 90 days. A Bayesian fixed-effect network meta-analysis was conducted.Results A total of 2131 participants from seven RCTs were included. IAT increased the proportion of mRS 0–1 at 90 days (RR 1.23, 95% CI 1.11 to 1.36), while the risk of sICH (RR 1.17, 95% CI 0.79 to 1.73) and 90-day mortality (RR 1.00, 95% CI 0.83 to 1.19) were comparable between groups. Furthermore, our network meta-analysis showed that intra-arterial alteplase (OR 1.94, 95% credible interval (CrI) 1.33 to 2.89) and TNK (OR 1.40, 95% CrI 1.10 to 1.77) showed favourable efficacy signals for mRS 0–1 compared with best medical treatment, whereas urokinase did not (OR 1.22, 95% CrI 0.86 to 1.73). No IAT regimen improved mRS 0–2, and safety outcomes were similar across treatments.Conclusions Adjunctive IAT was associated with a higher likelihood of excellent functional outcome, with no significant increase in sICH or mortality. Alteplase and TNK showed favourable efficacy signals, warranting further investigation in clinical trials.