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A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke

Why this mattered

Before MR CLEAN, endovascular stroke therapy had a plausible mechanism but an unsettled clinical status: opening an occluded large artery was technically possible, yet randomized evidence had not shown that doing so reliably improved disability. This trial changed that evidentiary balance. By requiring vessel-imaging confirmation of a proximal anterior-circulation occlusion and testing intraarterial therapy on top of usual care, mostly after intravenous alteplase, it showed a meaningful shift toward better 90-day functional outcomes without a significant increase in mortality or symptomatic intracerebral hemorrhage. The result made mechanical thrombectomy, then largely performed with retrievable stents, no longer just a revascularization procedure but a proven disability-reducing treatment for selected acute ischemic strokes.

Its importance was also temporal. MR CLEAN was the first clearly positive modern randomized trial in this area, published online in December 2014 and followed in 2015 by other positive trials such as ESCAPE, EXTEND-IA, SWIFT PRIME, and REVASCAT. Together, these studies rapidly transformed stroke systems of care: emergency stroke evaluation increasingly centered on fast vascular imaging, identification of large-vessel occlusion, transfer pathways to thrombectomy-capable centers, and workflow metrics measured in minutes. The paper therefore helped shift acute stroke treatment from a model dominated by intravenous thrombolysis within a narrow time window to one in which image-selected endovascular reperfusion became a central therapeutic pathway.

The later breakthroughs in extended-window thrombectomy depended on this foundation. Trials such as DAWN and DEFUSE 3 did not merely ask whether removing clot could help; MR CLEAN and its contemporaries had already established that principle in early-presenting large-vessel occlusion. The subsequent question became how to select patients whose brain tissue remained salvageable beyond conventional time limits. In that sense, MR CLEAN opened the modern era of endovascular stroke medicine: it made benefit demonstrable, made systems redesign urgent, and made later imaging-based expansion of eligibility scientifically and clinically credible.

Abstract

BACKGROUND: In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion, intraarterial treatment is highly effective for emergency revascularization. However, proof of a beneficial effect on functional outcome is lacking. METHODS: We randomly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone. Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset. The primary outcome was the modified Rankin scale score at 90 days; this categorical scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death). The treatment effect was estimated with ordinal logistic regression as a common odds ratio, adjusted for prespecified prognostic factors. The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores, as compared with usual care alone (shift analysis). RESULTS: We enrolled 500 patients at 16 medical centers in The Netherlands (233 assigned to intraarterial treatment and 267 to usual care alone). The mean age was 65 years (range, 23 to 96), and 445 patients (89.0%) were treated with intravenous alteplase before randomization. Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to intraarterial treatment. The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.30). There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs. 19.1%). There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage. CONCLUSIONS: In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe. (Funded by the Dutch Heart Foundation and others; MR CLEAN Netherlands Trial Registry number, NTR1804, and Current Controlled Trials number, ISRCTN10888758.).

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