Endovascular therapy after intravenous t-PA versus t-PA alone for stroke

Abstract

Background: Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic stroke, but whether a combined approach is more effective than intravenous t-PA alone is uncertain.

Methods: We randomly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone, in a 2:1 ratio. The primary outcome measure was a modified Rankin scale score of 2 or less (indicating functional independence) at 90 days (scores range from 0 to 6, with higher scores indicating greater disability).

Results: The study was stopped early because of futility after 656 participants had undergone randomization (434 patients to endovascular therapy and 222 to intravenous t-PA alone). The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment (40.8% with endovascular therapy and 38.7% with intravenous t-PA; absolute adjusted difference, 1.5 percentage points; 95% confidence interval [CI], -6.1 to 9.1, with adjustment for the National Institutes of Health Stroke Scale [NIHSS] score [8-19, indicating moderately severe stroke, or ≥20, indicating severe stroke]), nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher (6.8 percentage points; 95% CI, -4.4 to 18.1) and those with a score of 19 or lower (-1.0 percentage point; 95% CI, -10.8 to 8.8). Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days (19.1% and 21.6%, respectively; P=0.52) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P=0.83).

Conclusions: The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA, as compared with intravenous t-PA alone. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00359424.).

Figure 1. Distribution of Modified Rankin Scores, According to Study Group and Score on the National Institutes of Health Stroke Scale (NIHSS)

The percentages of patients are shown in or above each cell, according to score on the modified Rankin scale. Scores range from 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability (able to carry out all usual activities, despite some symptoms), 2 slight disability (able to look after own affairs without assistance but unable to carry out all previous activities), 3 moderate disability (requires some help but able to walk unassisted), 4 moderately severe disability (unable to attend to bodily needs without assistance and unable to walk unassisted), 5 severe disability (requires constant nursing care and attention, bedridden, and incontinent), and 6 death. Persons with a score of 0, 1, or 2 are considered to be functionally independent. Prespecified secondary analyses showed no significant differences between the two treatment groups across the entire distribution of the modified Rankin score overall (P = 0.25); among patients with an NIHSS score of 8 to 19, indicating moderately severe stroke (P = 0.83); or among those with an NIHSS score of 20 or more, indicating severe stroke (P = 0.06). The abbreviation t-PA denotes tissue plasminogen activator.

Figure 2. Adjusted Relative Risk for Predefined Subgroups, as Assessed According to the Primary Outcome of a Modified Rankin Score of 0 to 2 at 90 Days

Data were adjusted for age (continuous), baseline NIHSS strata, and time from onset to initiation of intravenous t-PA (continuous). The comparisons of baseline NIHSS strata were not adjusted for baseline NIHSS score, and the subgroups defined according to the baseline NIHSS strata and time from onset to intravenous t-PA were adjusted only for age. One patient who underwent randomization did not receive intravenous t-PA but was included in the intention-to-treat analysis. The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) allows for the systematic assessment of 10 regions of the brain with the use of computed tomography (CT), with a score of 1 indicating a normal region and 0 indicating a region showing signs of ischemia; total scores range from 10 (no evidence of early ischemia) to 0 (all 10 regions in the hemisphere show early ischemic changes). Data on ASPECTS were obtained for patients who had original CT scans for comparison. A total of 220 participants had an occlusion of the internal carotid artery (ICA), middle cerebral artery (M1), or basilar artery, as determined by means of CT angiography prior to treatment with intravenous t-PA.