Arterial collateral status and treatment effect of intravenous alteplase thrombolysis prior to endovascular treatment in patients with anterior circulation large vessel occlusion: Prespecified analysis of the MR CLEAN-NO IV trial

Background and purpose: Collateral blood flow to the affected cerebral territory in acute ischemic stroke may modify the effect of intravenous alteplase treatment (IVT) prior to endovascular treatment (EVT). We assessed whether an interaction effect between arterial collateral status, assessed by both a visual and quantitative collateral score (CS), and administration of IVT plus EVT was present in the MR CLEAN-NO IV trial. Methods: Baseline CT or MR angiography (CTA and MRA) from patients included in MR CLEAN-NO IV was assessed using both a visual and automated quantitative score for arterial collateral status. We included 526 patients with visual CS and 401 with quantitative CS in this prespecified analysis. The primary outcome was functional outcome measured as the modified Rankin Scale score at 90 days. Interaction terms of treatment allocation (IVT plus EVT vs EVT alone) and collateral scores were included in regression models to assess whether the treatment effect of IVT differed by arterial collateral status. Results: IVT plus EVT was not statistically significantly associated with better functional outcome compared with EVT alone (adjusted common odds ratio 1.14; 95% CI 0.84 to 1.55). There was no statistically significant modification of IVT treatment effect on functional outcome by either visual or quantitative CS (adjusted p-interaction=0.34; adjusted p-interaction=0.57, respectively). Conclusion: In the MR CLEAN-NO IV trial, we did not find evidence that arterial collateral status measured with a visual score or quantitative score can inform treatment decisions regarding IVT plus EVT for patients with acute ischemic stroke due to large vessel occlusion in the anterior circulation within 4.5 hours.