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IV Thrombolysis + Thrombectomy vs. Thrombectomy Alone for Acute Ischemic Stroke
Quick Takes
- Among patients with an anterior-circulation large-vessel occlusion stroke who presented directly to endovascular treatment centers, the benefit associated with intravenous thrombolysis (IVT) in the setting of endovascular thrombectomy was time dependent.
- There was a significant benefit associated with IVT plus thrombectomy compared with thrombectomy alone if the time between symptom onset and expected administration of IVT was within 2 hours 20 minutes.
- These data suggest that the benefit associated with IVT prior to thrombectomy was time dependent and lessened with longer times between symptom onset and expected administration of IVT.
Study Questions:
What is the association of treatment with intravenous thrombolysis (IVT) plus thrombectomy versus thrombectomy alone and outcomes modification by the time from stroke symptom onset to treatment?
Methods:
The investigators analyzed individual participant data in a meta-analysis from six randomized clinical trials comparing IVT plus thrombectomy versus thrombectomy alone. Enrollment was between January 2017 and July 2021 at 190 sites in 15 countries. All participants were eligible for IVT and thrombectomy and presented directly at thrombectomy-capable stroke centers (n = 2,334). For this meta-analysis, only patients with an anterior circulation large-vessel occlusion were included (n = 2,313). Interval from stroke symptom onset to expected administration of IVT and treatment with IVT plus thrombectomy versus thrombectomy alone was collected.
The primary outcome analysis tested whether the association between the allocated treatment (IVT plus thrombectomy vs. thrombectomy alone) and disability at 90 days (7-level modified Rankin Scale [mRS] score range, 0 [no symptoms] to 6 [death]; minimal clinically important difference for the rates of mRS scores of 0-2: 1.3%) varied with times from symptom onset to expected administration of IVT. The analysis was performed using mixed-effects ordinal regression (cumulative link mixed model) to test for an interaction between the treatment allocation and the time from symptom onset to expected administration of IVT and to calculate the odds of a 1-point shift on the mRS score in the direction of better outcomes, which was expressed with the adjusted common odds ratio (OR).
Results:
In 2,313 participants (1,160 in IVT plus thrombectomy group vs. 1,153 in thrombectomy alone group; median age, 71 [IQR, 62-78] years; 44.3% were female), the median time from symptom onset to expected administration of IVT was 2 hours 28 minutes (IQR, 1 hour 46 minutes to 3 hours 17 minutes). There was a statistically significant interaction between the time from symptom onset to expected administration of IVT and the association of allocated treatment with functional outcomes (ratio of adjusted common OR per 1-hour delay, 0.84; 95% confidence interval [CI], 0.72-0.97; p = 0.02 for interaction).
The benefit of IVT plus thrombectomy decreased with longer times from symptom onset to expected administration of IVT (adjusted common OR for a 1-step mRS score shift toward improvement, 1.49 [95% CI, 1.13-1.96] at 1 hour, 1.25 [95% CI, 1.04-1.49] at 2 hours, and 1.04 [95% CI, 0.88-1.23] at 3 hours). For an mRS score of 0, 1, or 2, the predicted absolute risk difference was 9% (95% CI, 3-16%) at 1 hour, 5% (95% CI, 1-9%) at 2 hours, and 1% (95% CI, -3% to 5%) at 3 hours. After 2 hours 20 minutes, the benefit associated with IVT plus thrombectomy was not statistically significant and the point estimate crossed the null association at 3 hours 14 minutes.
Conclusions:
The authors report that the benefit associated with IVT plus thrombectomy versus thrombectomy alone was time dependent and significant only if the time from symptom onset to expected administration of IVT was short.
Perspective:
This analysis reports that among patients with an anterior-circulation large-vessel occlusion stroke who presented directly to endovascular treatment centers, the benefit associated with IVT in the setting of endovascular thrombectomy was time dependent. Specifically, there was a significant benefit associated with IVT plus thrombectomy compared with thrombectomy alone if the time between symptom onset and expected administration of IVT was within 2 hours 20 minutes. These data suggest that the benefit associated with IVT prior to thrombectomy was time dependent and lessened with longer times between symptom onset and expected administration of IVT. The mechanism by which IVT was associated with increased odds for better functional outcomes in the early time window requires further research to elucidate the role of different contributors to the interaction observed.
Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Vascular Medicine, Interventions and Vascular Medicine
Keywords: Ischemic Stroke, Thrombolytic Therapy, Thrombectomy
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