Adjunctive Thrombolytics After Successful Endovascular Reperfusion: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objective: The efficacy and safety of intra-arterial thrombolysis (IAT) as an adjunct to endovascular thrombectomy (EVT) in large vessel occlusion strokes (LVOS) remain uncertain, with recent randomized controlled trials (RCTs) yielding conflicting results. This meta-analysis aimed to assess the impact of IAT following successful EVT in patients with LVOS.

Methods: A comprehensive search was conducted across PubMed, ClinicalTrials.gov, the Cochrane Library databases, and the International Stroke Conference 2025 abstracts to identify RCTs evaluating IAT following successful EVT from January 2015 to February 2025. The primary outcome was the odds of achieving an excellent functional outcome (defined as a modified Rankin Scale [mRS] = 0-1 at 90 days). Secondary outcomes included 90-day functional independence (mRS = 0-2). Safety measures included symptomatic intracranial hemorrhage (sICH), and mortality at 90 days. The protocol was registered in PROSPERO (CRD420250651602).

Results: The primary pooled analysis of 6 RCTs (N = 1,974) showed that IAT significantly increased the likelihood of achieving excellent functional outcome at 90 days (mRS = 0-1: odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.21-1.80, p < 0.001), with a notable effect in anterior circulation (OR = 1.48, 95% CI = 1.18-1.87, p < 0.001) but not in posterior circulation LVOS (OR = 1.51, 95% CI = 0.83-2.74, p = 0.18). Among thrombolytic drugs, alteplase was most strongly associated with favorable outcomes (mRS = 0-1: OR = 1.94, 95% CI = 1.31-2.87, p < 0.001), followed by tenecteplase (OR = 1.43, 95% CI = 1.08-1.89, p = 0.01). No significant safety concerns were observed, as there was no increase in the odds of sICH (OR = 1.15, 95% CI = 0.75-1.75, p = 0.51) or 90-day mortality (OR = 1.00, 95% CI = 0.79-1.26, p = 0.99). Sensitivity analyses for all outcomes yielded consistent results.

Interpretation: IAT following successful EVT significantly enhances the likelihood of achieving an excellent functional outcome, particularly in anterior circulation strokes. Although the benefit in posterior circulation strokes remains uncertain, the lack of significant differences in sICH risk and mortality across thrombolytic drugs and stroke locations support the safety of IAT. ANN NEUROL 2025.