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Stroke etiology does not modify the efficacy of intravenous thrombolysis before endovascular treatmentAdding clot-busting drugs to stroke treatment shows consistent results

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Key Takeaway
Note that stroke etiology does not modify the efficacy or safety of IVT combined with EVT for LVO patients.

This meta-analysis analyzed data from 6 RCTs involving 2313 patients with acute ischemic stroke due to large vessel occlusion (LVO) presenting directly to EVT-capable centers within 4.5 hours of onset. The study evaluated the impact of adding intravenous thrombolysis (IVT) to endovascular treatment (EVT) compared to EVT alone, specifically looking at whether stroke etiology influenced outcomes.

The primary finding was that there was no evidence of treatment effect modification by stroke etiologies for 90-day functional outcomes (P for interaction = 0.60). While a specific subgroup with other or undetermined etiology showed an improved 90-day functional prognosis with IVT plus EVT (1.34; 95% CI [1.05-1.69]), the authors note this finding is not robust and requires confirmation.

Safety outcomes also showed no treatment effect modification by stroke etiology. The results suggest that for patients presenting directly to EVT-capable centers, the addition of IVT provides consistent benefits regardless of the underlying cause of the stroke. Clinical application is limited by the need for more evidence regarding the specific undetermined subgroup.

How this fits prior evidence

This meta-analysis confirms and extends previous findings regarding bridging therapy in large vessel occlusion (LVO) stroke. It specifically addresses whether stroke etiology influences the efficacy of IVT before EVT, finding no significant interaction between etiology and outcome. This builds upon prior coverage showing that bridging therapy improves outcomes compared to EVT alone, while also noting that timing and location may influence results in different clinical windows.

When someone suffers a major stroke, every minute counts. Doctors often use a combination of two treatments: a clot-busting drug given through an IV and a surgical procedure to clear the blockage. A large review of data from over 2,300 patients looked at whether the specific cause of the stroke changed how well this combined treatment worked.

The results showed that the combination of the medication and surgery provided consistent benefits for patients with large vessel occlusions. Specifically, the study found that the underlying reason for the stroke did not change the overall success rate or the safety of the treatment. This means the dual approach works reliably across different types of stroke cases.

One small finding showed a potential benefit for a specific group whose stroke cause was unknown or listed as other. However, because this group is small and specific, experts say more research is needed to confirm that exact result. For now, the main takeaway is that combining these treatments provides a steady path toward better recovery.

What this means for you:
Combining clot-busting drugs with surgery helps stroke patients regardless of what caused their stroke.

Common questions

Does the cause of a stroke change how well treatment works?

The study found no evidence that the specific cause or reason for a stroke changed the effectiveness or safety of combining clot-busting medication with surgical treatment. For patients with large vessel occlusions, this combination remains a consistent approach regardless of what triggered the stroke.

Is it safe to use both drugs and surgery together?

The data showed that the safety of the treatment did not change based on the cause of the stroke. For patients arriving at specialized centers within 4.5 hours of their symptoms, the combination of intravenous thrombolysis and endovascular treatment was consistent in its safety profile.

What are the results for patients with unknown stroke causes?

The study noted a potential improvement in outcomes for patients whose stroke cause was listed as other or undetermined. However, this specific finding is not yet robust and requires more confirmation before it can be confirmed as a standard result.

Study Details

Study typeMeta analysis
Sample sizen = 2,313
EvidenceLevel 1
PublishedJul 2026
View Original Abstract ↓
OBJECTIVE: The benefit of intravenous thrombolysis (IVT) before endovascular treatment (EVT) in patients with acute ischemic stroke due to large vessel occlusion (LVO) who present directly to EVT-capable centers remains uncertain, and the effect may differ according to underlying stroke etiology. We assessed whether the benefit of IVT plus EVT versus EVT alone varied by stroke etiologies (large-artery atherosclerosis, cardioembolism, or other/undetermined). METHODS: We performed an individual participant data meta-analysis of 6 randomized controlled trials (RCTs) that compared IVT plus EVT to EVT alone in patients with LVO within 4.5 hours of stroke onset or time last known well. The heterogeneity of treatment effect was assessed using ordinal logistic regression models with interaction terms for stroke etiology and treatment in the intention-to-treat population, followed by subsequent mixed-effects meta-analysis. An additional analysis was performed to assess whether the treatment effect of IVT plus EVT differed by atrial fibrillation status. RESULTS: Among 2,313 eligible patients from 6 RCTs, 1,160 were randomized to the IVT plus EVT group and 1,153 to the EVT alone group. Median age was 71 years (interquartile range [IQR] = 62-78 years), and 44.3% of patients were women. Stroke etiology was classified as cardioembolism in 977 of 2,313 patients (42%), large artery atherosclerosis in 430 (19%), and other or unknown/undetermined in 906 (39%). No evidence of treatment effect modification by stroke etiologies on the association between IVT and 90-day functional outcome was observed (P for interaction = 0.60). For patients with other/undetermined stroke etiology, IVT plus EVT was associated with better 90-day functional prognosis (adjusted common odds ratio for a lower level of disability = 1.34, 95% confidence interval [CI] = 1.05-1.69). No treatment effect modification by stroke etiology was found for safety outcomes. No treatment effect heterogeneity by atrial fibrillation was found for all outcomes. INTERPRETATION: Among patients with LVO presenting directly to EVT-capable centers, stroke etiologies do not modify the overall efficacy or safety of IVT before EVT. The isolated benefit observed in the other/undetermined subgroup requires confirmation. ANN NEUROL 2026;100:180-190.
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