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Alteplase administered intravenously within 4.5 hours after onset of symptoms is the only reperfusion therapy with proven efficacy in patients with ischemic stroke. However, symptomatic intracranial hemorrhage, a devastating complication of intravenous thrombolysis treatment, may occur.1 In addition, there are multiple limitations to its use such as the narrow therapeutic time window required and the contraindications to its use such as recent surgery, coagulation abnormalities and a history of intracranial hemorrhage, etc.2 Despite its efficacy, intravenous alteplase is less effective at opening proximal occlusions of the major intracranial arteries. On the contrary, intraarterial therapy, including either a chemical dissolution of clots with thrombolytics or thrombectomy with mechanical devices, is highly effective for emergency revascularization in patients with a proximal intracranial arterial occlusion. The effect on functional outcomes however is lacking. 

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The authors of this Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) sought to assess whether intraarterial treatment within 6 hours after onset of symptoms plus usual care would be more effective than usual care alone in patients with a proximal arterial occlusion in the anterior cerebral circulation.3  It is a randomized, open-label, multicenter clinical trial done in 16 centers in the Netherlands. Intraarterial treatment (intraarterial thrombolysis, mechanical treatment, or both) plus usual care (including the use of intravenous administration of alteplase, if needed) was compared with usual care alone in patients with a proximal intracranial arterial occlusion. Eligible adult patients were those who had an occlusion of the distal intracranial carotid artery, middle cerebral artery or anterior cerebral artery, established with computed tomographic (CT) angiography (CTA), magnetic resonance angiography (MRA), or digital-subtraction angiography (DSA), and a score of 2 or higher on the National Institutes of Health Stroke Scale (NIHSS; range, 0 to 42, with higher scores indicating more severe neurologic deficits).

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Intraarterial treatment consisted of arterial catheterization with a microcatheter to the level of occlusion and the delivery of a thrombolytic agent, mechanical thrombectomy, or both. The maximum doses of intraarterial thrombolytic therapy if used was alteplase 90 mg, urokinase 1,200,000 IU and restricted to 30 mg of alteplase or 400,000 IU of urokinase if intravenous alteplase was given. Mechanical treatment could involve thrombus retraction, aspiration, wire disruption, or use of a retrievable stent. The primary outcome was the score on the modified Rankin scale at 90 days. The modified Rankin scale is a 7-point scale ranging from 0 (no symptoms) to 6 (death). A score of 2 or less indicates functional independence.4

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A total of 502 patients underwent randomization between December 2010 and March 2014. Intravenous alteplase was administered to 445 patients (89.0%) before randomization. Out of the 502 patients, only 233 patients (46.6%) were randomized to the intervention group and 267 patients (53.4%) were assigned to the control group.  Actual intraarterial therapy (with or without mechanical thrombectomy) was performed in ...

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