Intravenous alteplase before endovascular treatment does not improve acute ischemic stroke outcomes

1. Patients receiving intravenous alteplase before endovascular treatment had similar disability outcomes of symptomatic intracerebral hemorrhage post-stroke compared to patients not receiving alteplase.

2. The incidence of symptomatic intracerebral hemorrhage post-stroke is similar between patients receiving intravenous alteplase before endovascular treatment and patients not receiving alteplase.

Evidence Rating Level: 1 (Excellent)       

Study Rundown: Endovascular treatment (EVT) is currently the standard of care for patients with acute ischemic stroke due to intracranial vessel occlusion. Some evidence suggests that pre-administration of intravenous alteplase, a thrombolytic medication, may help improve outcomes. In this randomized control trial, patients who had an acute ischemic stroke due to an intracranial proximal occlusion of the anterior circulation were randomized to either receive intravenous alteplase before EVT, or EVT alone. The primary outcome was the functional assessment by modified Rankin scale at 90 days post-treatment. Secondary endpoints assessed the success of cranial reperfusion, decrease in lesion volume on imaging, and quality of life indicators. The study found no significant change in the modified Rankin scale scores between the groups. All other secondary measures also yielded no significant differences between the two patient cohorts. With respect to safety data, mortality was slightly higher in the EVT-alone group and no differences were found in the incidence of symptomatic intracerebral hemorrhage. Overall, the data does not support the addition of alteplase to the standard of care of EVT for patients with acute ischemic stroke. The conclusions of this trial are limited by patient selection as EVT was readily available for all patients in this study, potentially leaving a role of alteplase in more remote stroke scenarios.

Click to read the study in NEJM

Relevant Reading: Preceding intravenous thrombolysis facilitates endovascular mechanical recanalization in large intracranial artery occlusion

In-Depth [randomized controlled trial]: In this multi-center, randomized control trial, 539 consenting patients with acute ischemic stroke due to an intracranial proximal occlusion of the anterior circulation were enrolled into the trial and randomized in a 1:1 ratio into two groups: one receiving 0.9mg/kg intravenous ateplase within 4.5 hours of symptom incidence prior to EVT or received EVT alone. The primary objective was to evaluate the superiority of alteplase on functional response as measured by the modified Rankin scale at 90 days follow-up by common odds ratio. The study found that no significant differences in median scores between groups (adjusted common OR: 0.84, 95%CI [0.62-1.15], P=0.28). Secondary outcomes assessed improved stroke outcomes such as the proportion of incidence of recanalization, reperfusion success, and quality of life measures. The analysis also found no significant differences in these measures between the two groups. The EVT-alone group experienced a slightly higher proportion of mortality within 90 days (20.5% vs. 15.8%, OR: 1.39, 95% CI [0.84-2.3]), but similar proportions of symptomatic intracerebral hemorrhage (5.9% vs. 5.3%, OR: 1.3, 95% CI [0.6-2.81]). All other safety endpoints and complications were not significantly different. Taken together, the study concludes that intravenous alteplase administration prior to EVT was not superior, nor non-inferior to the standard of care treatment regimen of EVT alone in improving functional outcomes within 90 days.

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