The question to thrombolyse eligible patient with Large Vessel Occlusion planned thrombectomy is always a daunting one. Studies has shown that IV Thrombolysis preceding endovascular thrombectomy has potential to improve reperfusion before and after the procedure. And also potential risk of bleeding.
Omar et al (j.amjcard.2026) did a meta analysis for safety and efficacy of thrombolysis prior to thrombectomy in LVO AIS. The study found that bridging therapy was associated with modest but statistically significant improvements in functional independence.
Bridging therapy was associated with a 31% increased risk of sICH, particularly in the full-dose alteplase group. This finding aligns with the known effects of IVT, including blood−brain barrier disruption,enhanced reperfusion injury, and increased hemorrhagic transformation, particularly in ischemic tissue
BRIDGE TNK (NEJM.2025) is an investigator‐initiated, multicenter, prospective, randomized, open‐label trial with blinded end point evaluation conducted at 40 thrombectomy‐capable centers in China. The study found that functional independence at 90 days was observed in 147 patients (52.9%) in the tenecteplase-thrombectomy group and 120 (44.1%) in thrombectomy alone group. Study concluded that IVT before thrombectomy in patients presenting within 4.5 hours resulted higher functional independence at 90 days.
DIRECT SAFE (Lancet. 2022) was an international, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Study was done to test the hypothesis that clinical outcome of ischemic stroke patients with intracranial internal carotid artery, middle cerebral artery or basilar artery occlusion treated with direct endovascular thrombectomy within 4.5 hours will be non-inferior compared with that of standard bridging IV thrombolysis (Alteplase or Tenecteplase) followed by endovascular thrombectomy. . Functional independence occurred in 80 (55%) of 146 patients in the direct thrombectomy group and 89 (61%) of 147 patients in the bridging therapy group.Safety outcomes were similar between groups, with symptomatic intracerebral haemorrhage occurring in two (1%) of 146 patients in the direct group and one (1%) of 147 patients in the bridging group. The study did not show non-inferiority of direct endovascular thrombectomy compared with bridging therapy.
SWIFT DIRECT Trail (Lancet. 2022) was done to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke.. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7·3%, 95% CI -16·6 to 2·1, lower limit of one-sided 95% CI -15·1%, crossing the non-inferiority margin of -12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy (risk difference -1·0%, 95% CI -4·8 to 2·7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [91%] of 201 vs 199 [96%] of 207, risk difference -5·1%, 95% CI -10·2 to 0·0, p=0·047). Study concluded that thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates.
DIRECT MT (NEJM.2020) conducted a trial at 41 academic tertiary care centers in China to evaluate endovascular thrombectomy with or without intravenous alteplase in patients with acute ischemic stroke. In Chinese patients with acute ischemic stroke from large-vessel occlusion, endovascular thrombectomy alone was noninferior with regard to functional outcome, within a 20% margin of confidence, to endovascular thrombectomy preceded by intravenous alteplase administered within 4.5 hours after symptom onset.
ATTENTION LATE Trial (JAMA.2026) is a multicentre, open label, blinded end point, RCT done in 40 centres in china. Study was done to evaluate the efficacy and safety of intravenous tenecteplase before EVT vs EVT alone in patients with moderate to severe basilar artery occlusion admitted within 4.5 to 24 hours from stroke onset.In this randomized clinical trial that included 330 participants (329 completed follow-up), 50 of 165 participants (30%) who received tenecteplase prior to endovascular thrombectomy vs 50 of 164 (30%) who did not receive tenecteplase achieved functional independence at 90 days (adjusted rate ratio, 0.92). The study concluded that addition of tenecteplase before endovascular thrombectomy did not lead to significant functional improvement.
How does IVT before EVT Beneficial ?
- Bridging therapy was associated with higher rates o sucessful reperfusion, functional independence and lower rate of mortality at 90 days.
- IVT produces systemic fibrinolysis state promoting early microvascular reperfusion, softening thrombus composition, lysing distal emboli inaccessible to thrombectomy devices, and limiting infarct core expansion before mechanical retrieval.
- Even when successful recanalization is ultimately achieved, improved microcirculatory flow may translate into better neurological recovery.
Recommendation
- ASA 2026 Guidelines recommends IVT in all eligible patients before thrombectomy to improve overall reperfusion efficacy and clinical outcomes.
- Usefulness of IVT in the extended window period of 4.5 - 24 hours is less certain.
Reference
- Omer Mohammed et al. The American Journal of Cardiology,Safety and Efficacy of Thrombolysis Prior to Thrombectomy in Large-Vessel Acute Ischemic Stroke: An Updated Systematic Review and Meta-Analysis.
