Addition of Intra-arterial Treatment within 6 Hours of Stroke Onset to Usual Care Improves Functional Outcomes in Patients with Acute Ischemic Stroke Due to a Proximal Intracranial Occlusion of the Anterior Circulation

EBM Focus - Volume 9, Issue 51

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Reference: MR CLEAN trial (N Engl J Med 2014 Dec 17 early online) (level 1 [likely reliable] evidence)

Stroke is a major cause of death and disability worldwide, but administration of intravenous alteplase within 3-4.5 hours of symptom onset is currently the only recommended reperfusion therapy for patients with acute ischemic stroke (Stroke 2013 Mar;44(3):870, NICE 2012 Sep:TA264). Intravenous alteplase treatment has many contraindications, however, and its effectiveness may depend upon the location of the occlusion (JAMA 2004 Oct 20;292(15):1839, JAMA Neurol 2014 Feb;71(2):151). A recent randomized trial compared intra-arterial treatment plus usual care vs. usual care alone in 502 patients (mean age 65 years) with acute ischemic stroke due to proximal arterial occlusion in the anterior cerebral circulation.

All patients eligible for randomization had occlusion confirmed on vessel imaging and could be treated within 6 hours of stroke onset. Intravenous alteplase was allowed as part of usual care and 89% of patients received alteplase before randomization. Intra-arterial therapy consisted of arterial catheterization with a microcatheter to the occlusion plus delivery of a thrombolytic agent, mechanical thrombectomy (thrombus retraction, aspiration, wire disruption, or retrievable stent), or both. Actual intra-arterial therapy was only performed in 84.1% of the 233 patients randomized to this intervention, 96.9% of whom had mechanical treatment with retrievable stents. Intra-arterial thrombolytics were used in 10.3% of patients randomized to intra-arterial treatment, but only 1 patient received intra-arterial thrombolytics alone. Arterial recanalization was observed on imaging 24-hours after treatment in 75.4% in the intra-arterial treatment group vs. 32.9% in the usual care group (p < 0.05). At 90-days post-treatment, 32.6% of patients in the intra-arterial treatment group had a modified Rankin score of 0-2 compared to 19.1% of patients in the usual care group (adjusted odds ratio 2.16, 95% CI 1.39-3.38 NNT 8). Intra-arterial treatment was also associated with significantly more patients experiencing no disability interfering with daily activities at 90 days as measured by a score of 19-20 on the Barthel index (46% vs. 29.8%, p < 0.05 NNT 7). There were no significant differences between groups in any serious adverse events or mortality, however intra-arterial treatment was associated with an increased rate of new ischemic stroke at different vascular territory (5.6% vs. 0.4%, p < 0.001 NNH 19).

The results of this trial suggest that intra-arterial treatment may significantly improve functional outcomes in patients with acute ischemic stroke due to proximal arterial occlusion in anterior cerebral circulation. Previous randomized trials have found no significant improvement with intra-arterial therapy compared to intravenous alteplase alone (N Engl J Med 2013 Mar 7;368(10):904, N Engl J Med 2013 Mar 7;368(10):914, N Engl J Med 2013 Mar 7;368(10):893). However, the methodology of these trials varied considerably. One trial did not allow intravenous alteplase before endovascular treatment, instead using heparin during angiography, and using a micro-guidewire for clot disruption with few patients receiving retrievable stents (N Engl J Med 2013 Mar 7;368(10):904). Another smaller trial performed mechanical embolectomy with a coil retriever or aspiration device (N Engl J Med 2013 Mar 7;368(10):914), while the final trial mainly used these devices and did not have radiologically proven occlusions in all patients (N Engl J Med 2013 Mar 7;368(10):893). The retrievable stents used in the current trial have been shown to be more effective than Merci coil retrievers used in the previous trials (Lancet 2012 Oct 6;380(9849):1231, Lancet 2012 Oct 6;380(9849):1241). Rather than this trial contradicting earlier findings, it seems that this represents an improvement in the approach to intra-arterial therapy to the point where it now may become another component of the management of patients with acute stroke.

For more information, see the Endovascular therapy for acute stroke topic in DynaMed.