Intra-Arterial Thrombolysis Following Endovascular Recanalization for Large Vessel Occlusion Stroke: A Systematic Review and Meta-Analysis

Abstract

Background and objectives: This systematic review and meta-analysis aims to evaluate the treatment effects of intra-arterial thrombolysis (IAT) after endovascular recanalization in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Endovascular recanalization is the standard treatment for large vessel occlusion (LVO) stroke. Despite successful reperfusion after thrombectomy, fewer than half of the patients regain functional independence at 90 days, highlighting the potential role of impaired microcirculation in poor neurologic outcomes. The efficacy and safety of intra-arterial thrombolysis (IAT) after endovascular recanalization remains controversial. This systematic review and meta-analysis aims to evaluate the treatment effects of IAT after endovascular recanalization in patients with acute ischemic stroke (AIS) due to LVO.

Methods: We conducted a study-level systematic review and meta-analysis based on PubMed, Embase, CENTRAL, and ClinicalTrials.gov from database inception to February 8, 2025. Only randomized controlled trials (RCTs) reporting the efficacy and safety of IAT after endovascular recanalization in large vessel occlusion stroke were included. The risk of bias of the included studies was assessed using the Risk of Bias 2 tool. The pooled data were analyzed using a random-effects meta-analysis. Our primary outcome was the proportion of patients with modified Rankin Scale (mRS) scores 0-1 at 90 days. Other outcomes included the proportion of patients with mRS scores 0-2 at 90 days, all-cause mortality at 90 days, and symptomatic intracranial hemorrhage and any intracranial hemorrhage within 48 hours. The study protocol was registered on PROSPERO (CRD42025639519).

Results: A total of 6 RCTs with 1,985 initially enrolled patients were included in the analysis. A higher proportion of mRS scores 0-1 at 90 days was observed in the IAT group (risk ratio [RR] 1.25, 95% CI 1.11-1.41). No significant differences were found in the proportion of mRS scores 0-2 at 90 days (RR 1.04, 95% CI 0.96-1.13) between the groups. Regarding safety outcomes, 90-day all-cause mortality (RR 1.00, 95% CI 0.83-1.21), symptomatic intracranial hemorrhage (RR 1.14, 95% CI 0.76-1.70), and any intracranial hemorrhage (RR 1.16, 95% CI 0.98-1.37) were similar in the IAT group and control group.

Discussion: Among patients with AIS due to LVO, IAT after endovascular recanalization adds additional benefits to functional outcomes, with no increased risk of death or intracranial hemorrhage.

Figure 1. Study Flow Diagram

Figure 2. Meta-Analysis Forest Plot for mRS Scores 0–1 at 90 Days and mRS Scores 0–2 at 90 Days

ANGEL-TNK = Intra-arterial Tenecteplase After Successful Endovascular Therapy; ATTENTION = Intra-Arterial Tenecteplase after Successful Endovascular Recanalisation in Patients with Acute Posterior Circulation Arterial Occlusion; CHOICE = Chemical Optimization of Cerebral Embolectomy; mRS = modified Rankin Scale; PEARL = Intra-arterial Alteplase for Acute Ischaemic Stroke After Mechanical Thrombectomy; POST-TNK = Adjunctive Intra-arterial Tenecteplase Following Near-Complete to Complete Reperfusion for Large Vessel Occlusion Stroke; POST-UK = Adjunctive Intra-Arterial Urokinase After Near-Complete to Complete Reperfusion for Acute Ischemic Stroke.

Figure 3. Meta-Analysis Forest Plot for All-Cause Mortality at 90 Days, Symptomatic Intracranial Hemorrhage Within 48 Hours, and Any Intracranial Hemorrhage Within 48 Hours

*The data for clinically symptomatic or any intracranial hemorrhage were within 24 hours in the CHOICE trial. ANGEL-TNK = Intra-arterial Tenecteplase After Successful Endovascular Therapy; ATTENTION = Intra-Arterial Tenecteplase after Successful Endovascular Recanalisation in Patients with Acute Posterior Circulation Arterial Occlusion; CHOICE = Chemical Optimization of Cerebral Embolectomy; eTICI = expanded thrombolysis in cerebral infarction; PEARL = Intra-arterial Alteplase for Acute Ischaemic Stroke After Mechanical Thrombectomy; POST-TNK = Adjunctive Intra-arterial Tenecteplase Following Near-Complete to Complete Reperfusion for Large Vessel Occlusion Stroke; POST-UK = Adjunctive Intra-Arterial Urokinase After Near-Complete to Complete Reperfusion for Acute Ischemic Stroke.

Figure 4. Forest Plot of Age, Time From Stroke Onset to Randomization or Thrombectomy, Baseline NIHSS Score, Baseline Glucose, Cause of Stroke, Occlusion Site, and Angiographic eTICI Score for 90-Day mRS Scores 0–1

*POST-TNK and POST-UK use 69 years, ANGEL-TNK and PEARL use 65 years, and ATTENTION-IA uses 70 years as the cutoff point for age. **ANGEL-TNK and ATTENTION-IA use 360 minutes, CHOICE uses 436 minutes, POST-TNK uses 498 minutes, and POST-UK uses 524 minutes as the cutoff point for time from stroke onset to randomization or thrombectomy. ***POST-TNK and POST-UK use 15, ANGEL-TNK and PEARL use 16, and ATTENTION-IA uses 20 as the cutoff point for the NIHSS score. ANGEL-TNK = Intra-arterial Tenecteplase After Successful Endovascular Therapy; ATTENTION = Intra-Arterial Tenecteplase after Successful Endovascular Recanalisation in Patients with Acute Posterior Circulation Arterial Occlusion; CHOICE = Chemical Optimization of Cerebral Embolectomy; NIHSS = NIH Stroke Scale; PEARL = Intra-arterial Alteplase for Acute Ischaemic Stroke After Mechanical Thrombectomy; POST-TNK = Adjunctive Intra-arterial Tenecteplase Following Near-Complete to Complete Reperfusion for Large Vessel Occlusion Stroke; POST-UK = Adjunctive Intra-Arterial Urokinase After Near-Complete to Complete Reperfusion for Acute Ischemic Stroke.