Endovascular treatment for acute ischemic stroke

Abstract

Background: In patients with ischemic stroke, endovascular treatment results in a higher rate of recanalization of the affected cerebral artery than systemic intravenous thrombolytic therapy. However, comparison of the clinical efficacy of the two approaches is needed.

Methods: We randomly assigned 362 patients with acute ischemic stroke, within 4.5 hours after onset, to endovascular therapy (intraarterial thrombolysis with recombinant tissue plasminogen activator [t-PA], mechanical clot disruption or retrieval, or a combination of these approaches) or intravenous t-PA. Treatments were to be given as soon as possible after randomization. The primary outcome was survival free of disability (defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability despite symptoms, and 6 death) at 3 months.

Results: A total of 181 patients were assigned to receive endovascular therapy, and 181 intravenous t-PA. The median time from stroke onset to the start of treatment was 3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA (P<0.001). At 3 months, 55 patients in the endovascular-therapy group (30.4%) and 63 in the intravenous t-PA group (34.8%) were alive without disability (odds ratio adjusted for age, sex, stroke severity, and atrial fibrillation status at baseline, 0.71; 95% confidence interval, 0.44 to 1.14; P=0.16). Fatal or nonfatal symptomatic intracranial hemorrhage within 7 days occurred in 6% of the patients in each group, and there were no significant differences between groups in the rates of other serious adverse events or the case fatality rate.

Conclusions: The results of this trial in patients with acute ischemic stroke indicate that endovascular therapy is not superior to standard treatment with intravenous t-PA. (Funded by the Italian Medicines Agency, ClinicalTrials.gov number, NCT00640367.).

Figures

Figure 1. Modified Rankin Score at 3 Months According to Treatment Group

The primary outcome was disability-free survival at 3 months, with freedom from disability defined as a score of 0 or 1 on the modified Rankin scale (range, 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability despite symptoms, and 6 death). The number in each cell denotes the number of patients with that score. The statistical analysis plan specified dichotomized scores of 0 or 1 (good outcome) versus 2 to 6 (poor outcome). The proportion of patients with a modified Rankin score of 0 or 1 at 3 months was 30.4% with endovascular treatment and 34.8% with intravenous tissue plasminogen activator (t-PA). In the analysis adjusted for age, sex, stroke severity, and presence or absence of atrial fibrillation at baseline, the odds ratio with endovascular treatment was 0.71 (95% confidence interval, 0.44 to 1.14; P = 0.16).

Figure 2. Effect of Treatment on the Primary Outcome in Subgroups

The odds ratio in each subgroup was adjusted for the effects of the key variables (age, sex, initial stroke severity, and presence or absence of atrial fibrillation at baseline). Initial stroke severity was measured by means of the National Institutes of Health Stroke Scale (NIHSS; range, 0 to 42, with higher scores indicating more severe neurologic impairment; scores of ≤6 indicate mild impairment, and scores of ≥25 indicate very severe impairment). Age and NIHSS score were used as continuous variables. The variables chosen for multivariate and subgroup analyses were prespecified. The cutoff points for age, NIHSS score, and blood pressure were determined with the use of the Youden method, after a receiver-operating-characteristic analysis tabulating sensitivity, specificity, and accuracy for each possible cutoff point. For time to treatment, patients who did not receive the assigned treatment were excluded, and an additional patient in the endovascular-treatment group was excluded because the procedure was interrupted owing to equipment breakdown. For stroke cause and territory, the 2 patients with conditions mimicking stroke were excluded. For stroke territory, a third patient was excluded because the stroke was in both the posterior and anterior circulation. The analysis of major protocol deviations, and all the other subgroup analyses, included the 12 patients at the center that was withdrawn from the study.