Mechanical Thrombectomy Outcomes With or Without Intravenous Thrombolysis

Insight From the ASTER Randomized Trial

Florent Gariel, MD, MSc; Bertrand Lapergue, MD, PhD; Romain Bourcier, MD, PhD; Jérôme Berge, MD; Xavier Barreau, MD; Mikael Mazighi, MD, PhD; Maéva Kyheng, BST; Julien Labreuche, BST; Robert Fahed, MD; Raphael Blanc, MD, MSc; Benjamin Gory, MD, PhD; Alain Duhamel, PhD; Suzana Saleme, MD; Vincent Costalat, MD, PhD; Serge Bracard, MD, PhD; Hubert Desal, MD, PhD; Lili Detraz, MD; Arturo Consoli, MD; Michel Piotin, MD, PhD; Gaultier Marnat, MD; for the ASTER Trial Investigators

Disclosures

Stroke. 2018;49(10):2383-2390. 

In This Article

Methods

Patient Selection

We performed here a post hoc analysis from the ASTER trial.[4,5] ASTER was a randomized, multicenter, open-label, blinded end point clinical trial of first-line CA versus first-line SR to determine the best recanalization strategy in patients with a proximal arterial occlusion in the anterior circulation demonstrated on vessel imaging and treatable within 6 hours after symptom onset. IVT was delivered according to recommendations of the American Stroke Association and European Stroke Organization[6,7] within 4.5 hours after onset of symptoms in the absence of contraindications. Contraindications for IVT were as follows: late treatment (between 4.5 and 6 hours after onset) and treatment in patients with a possible high bleeding risk after thrombolytic therapy, including elevated increased international normalized ratio (1.7–3.0), thrombocyte count <90×10[9]/L, history of intracerebral hemorrhage, severe head injury in the preceding 4 weeks, previous acute ischemic stroke in the preceding 6 weeks and major surgery, gastrointestinal bleeding, or urinary tract bleeding within the previous 2 weeks.

The study protocol and the consent form were approved by the Comité de Protection des Personnes Ile de France VI (ID 2015-A00830-49). According to French laws, oral informed consent was sought from patients if their level of consciousness was sufficient or else from a relative. This study operated an emergency inclusion protocol because of the nature of the condition.

This study enrolled adults admitted with ischemic stroke secondary to occlusion of the anterior circulation (carotid terminus or M1 or M2 segments) within 6 hours of symptom onset. Immediately after baseline brain imaging and before the endovascular procedure, patients were randomly allocated in a 1:1 fashion to undergo either CA (intervention) or SR (control) thrombectomy as the first-line intervention. The data that support the findings of this study are available from B.L. on reasonable request.

Outcomes

The primary outcome for this post hoc study was functional independence as defined by a 90-day modified Rankin Scale of ≤2. The secondary technical outcomes were the percentage of patients with successful revascularization defined as a modified Thrombolysis in Cerebral Infarction (mTICI) score of 2b or 3 at the end of angiography after all endovascular treatments, the percentage of patients with successful revascularization (mTICI 2b or 3) at the end of the first-line strategy, and the rate of MT requiring >2 device passes. The secondary clinical outcomes were the change in National Institutes of Health Stroke Scale (NIHSS) score at 24 hours, excellent outcome as defined by a 90-day modified Rankin Scale score of 0 or 1, and death because of any cause at 90 days. Intracranial hemorrhage rate was also reported as appreciated on imaging at 24 hours according to the European Cooperative Acute Stroke Study 3 classification,[8] and symptomatic intracranial hemorrhage at 24 hours, defined as any intracranial hemorrhage visualized on follow-up imaging and associated with a 4-point or greater worsening on the NIHSS score or that resulted in death. Adverse events also included procedure-related serious adverse events (arterial perforation, arterial dissection, embolization in a new vascular territory, subarachnoid hemorrhage, and vasospasm).

Statistical Analysis

Quantitative variables are expressed as means (SD) in the case of normal distribution or medians (interquartile range) otherwise. Categorical variables are expressed as numbers (percentage). Normality of distributions was assessed using histograms and the Shapiro-Wilk test. Baseline characteristics were described according to the study groups (combined IVT and MT [IVT+MT] versus MT alone [MT]), and absolute standardized differences were calculated to evaluate baseline imbalance; an absolute standardized difference >20% was interpreted as meaningful imbalance. Comparisons in binary outcomes between the 2 study groups were performed using generalized estimating equations models (Poisson distribution, log-link function) to take into account the center effect and including as covariate the allocated first-line MT strategy (CA versus SR); adjusted risk ratios (RRs) were derived from generalized estimating equations models as effect size using MT group as reference. Comparison in change in NIHSS score at 24 hours from admission was performed using a linear mixed model included admission NIHSS score and first-line MT strategy as fixed effects and center as random effect; adjusted between-group mean difference was derived from this model as effect size. Normality of model residuals was checked and satisfied. Comparisons in outcomes were further adjusted for prespecified confounding factors (age, hypertension, diabetes mellitus, admission NIHSS, and Alberta Stroke Program Early CT Scores, site of occlusion, onset to puncture time). Between-group comparisons in outcomes were further stratified according to the first-line MT strategy. Heterogeneity across first-line strategy subgroups was tested by introducing the multiplicative term between study groups and first-line MT strategy into the generalized estimating equations and linear mixed models. Our first analyses covered the whole study group; all analyses were repeated after excluding patients with anticoagulant medication before stroke onset to acknowledge the large between-group difference because effective anticoagulation is a contraindication for IVT.

Statistical testing was conducted at the 2-tailed α-level of 0.05. Data were analyzed using the SAS software version 9.4 (SAS Institute, Cary, NC).

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