Extracranial Carotid Disease and Effect of Intra-arterial Treatment in Patients With Proximal Anterior Circulation Stroke in MR CLEAN.

Berkhemer, Olvert A; Borst, Jordi; Kappelhof, Manon; Yoo, Albert J; van den Berg, Lucie A; Fransen, Puck S S; Beumer, Debbie; Schonewille, Wouter J; Nederkoorn, Paul J; Wermer, Marieke J H; Marquering, Henk A; Lingsma, Hester F; Roos, Yvo B W E M; van Oostenbrugge, Robert J; Dippel, Diederik W J; van Zwam, Wim H; Majoie, Charles B L M; Emmer, Bart J; van der Lugt, Aad

Background The presence of extracranial carotid disease (ECD) is associated with less favorable clinical outcomes in patients with acute ischemic stroke caused by intracranial proximal occlusion. Acute intra-arterial treatment (IAT) in the setting of extracranial and intracranial lesions is considered challenging, and whether it yields improved outcomes remains uncertain. Objective To examine whether the presence of ECD modified the effect of IAT for intracranial proximal anterior circulation occlusion. Design Prespecified subgroup analysis of a randomized clinical trial of endovascular treatment for acute ischemic stroke in the Netherlands. (Trial registrations: NTR1804 [Netherlands Trial Register] and ISRCTN10888758). Setting 16 hospitals in the Netherlands. Patients Acute ischemic stroke caused by proximal intracranial arterial occlusion of the anterior circulation. Extracranial carotid disease was defined as cervical internal carotid artery stenosis (>50%) or occlusion. Intervention IAT treatment versus no IAT. Measurements The primary outcome was functional outcome, as measured by the modified Rankin Scale at 90 days and reported as adjusted common odds ratio (acOR) for a shift in direction of a better outcome. Multivariable ordinal logistic regression analysis with an interaction term was used to estimate treatment effect modification by ECD. Results The overall acOR was 1.67 (95% CI, 1.21 to 2.30) in favor of the intervention. The acOR was 3.1 (CI, 1.7 to 5.8) in the prespecified subgroup of patients with ECD versus 1.3 (CI, 0.9 to 1.9) in patients presenting without ECD. Both acORs are in favor of the intervention (P for interaction = 0.07). Limitation The study was not powered for subgroup analysis. Conclusion Intra-arterial treatment may be at least as effective in patients with ECD as in those without ECD, and it should not be withheld in these complex patients with acute ischemic stroke. Primary Funding Source Dutch Heart Foundation, AngioCare BV, Medtronic/Covidien/EV3, MEDAC Gmbh/LAMEPRO, Penumbra, Stryker, and Top Medical/Concentric.