1. Among patients with large vessel ischemic stroke and evidence of salvageable brain tissue on computed tomography (CT) perfusion imaging, endovascular thrombectomy following intravenous (IV) alteplase administration improved technical reperfusion and both early clinical and late functional outcomes when compared to IV thrombolytic therapy alone.
2. No significant differences in risk, including mortality or intracerebral hemorrhage, were apparent between the treatment and control arms of the trial.
Evidence Rating Level: 1 (Excellent)
Study Rundown: The standard of care in the management of ischemic stroke has heretofore been reliant on the early administration of intravenous thrombolytics in an effort to dissolve the cerebral vascular occlusion and subsequently restore perfusion to at-risk tissue. Based on a similar logic to that applied when treating a patient with immediate stenting of a coronary vessel during an occlusive myocardial infarction, it has been proposed that early endovascular thrombectomy may advance stroke management by facilitating rapid reperfusion of at-risk brain tissue. However, the results of many prior studies have been contradictory, and optimal stoke patient management remains controversial. The current multicenter, randomized controlled trial—Extending the Time for Thrombolysis in Emergency Neurological Deficits – Intra-Arterial (EXTEND-IA)—sought to determine if IV thrombolysis plus endovascular thrombectomy improved outcomes for patients with acute anterior circulation strokes and a visible penumbra of salvageable brain tissue on perfusion imaging when compared to IV thrombolytic therapy alone. This study improved upon the design of prior trials through its standardized use of CT perfusion imaging to stratify patients’ candidacy for intraarterial therapy by identifying those with rescuable hypoperfused tissue as well as those with large irreversible areas of ischemia. As compared to the control arm, patients randomized to the endovascular therapy arm of the trial demonstrated a significant increase in reperfusion rates at 24 hours in addition to significant improvements in clinical neurologic improvement at three days and functional outcomes at 90 days without significant differences in mortality. The study was halted early due to the significance of its results. This introduced some limitations including a smaller sample size, which prevented proper subgroup analysis and introduced the possibility for overestimation of the intervention effect. Additionally, the study did not evaluate the effect of infarct location or size on the efficacy of endovascular therapy. The current trial demonstrated unequivocally that endovascular thrombectomy could significantly improve upon the current standard of stroke care for patients following proper selection with perfusion imaging, and further studies are warranted to characterize the effect of treatment variables such as infarct size, location, time-to-treatment and device type on patient outcomes.
Relevant Reading: A randomized trial of intraarterial treatment for acute ischemic stroke
In-Depth [randomized controlled trial]: Across 10 medical centers in Australia and New Zealand, 70 patients were enrolled and randomized in equal proportion to the control and the endovascular therapy arms of the trial. Baseline characteristics between the groups were not significantly different, with an average age of 70.2±11.8 and 68.6±12.3 years and an approximately equal gender dsitribution for the control and treatment arms, respectively. All patients underwent baseline standardized and automated CT perfusion imaging and were stratified for eligibility based two imaging criteria: the presence of an irreversibly damaged ischemic core of less than 70mL in volume and a region of rescuable, hypoperfused penumbral tissue, identified by a Tmax value of greater than six seconds. All patients received intravenous alteplase therapy within 4.5 hours of onset as per the standard of care for acute management of ischemic stroke. Those randomized to the treatment arm of then underwent baseline angiography and subsequent thrombolysis with a Solitaire FR stent retriever device within 6 hours of onset. Primary outcomes of the study were reperfusion of the penumbral region, defined as the reduction in penumbral volume between baseline imaging and that at 24 hours and clinical improvement at three days, defined as a >8 point reduction in the patient’s presenting National Institute of Health Stroke Scale (NIHSS). Secondary outcomes were functional outcomes at 90 days, particularly those defined as functional independence, or a modified Rankin scale score of <2. Roughly 25% of patients were excluded from randomization due to perfusion imaging criteria. As compared to those in the control arm, patients who underwent endovascular treatment demonstrated a significant increase in reperfusion at 24 hours (89% vs 34%, P < 0.001), early neurologic recovery at three days (OR 2.0, CI 1.2-3.8; P = 0.006) and an increased likelihood of functional independence at 90 days (71% vs. 40%, P = 0.01.) There were no significant differences in mortality between the two groups. There were two cases of symptomatic intracerebral hemorrhage in the control arm, and two cases of large parenchymal hematomas in the treatment arm, at least one of which was iatrogenic, and one case of distal embolization following intrarterial catheterization.
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