CHOICE RCT – Post-Thrombectomy tPA for Stroke

March 24, 2022

Written by Graham Van Schaik

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Among patients with acute ischemic stroke with large vessel occlusion (LVO) that have been successfully reperfused with thrombectomy, the use of post-thrombectomy adjunctive intra-arterial alteplase results in greater likelihood of excellent neurologic outcome at 90 days – modified-Rankin score (mRs) 0 or 1 – when compared with placebo.

Why does this matter?
Only 27% of patients with acute ischemic stroke and LVO who undergo successful reperfusion after mechanical thrombectomy are disability free at 3 months. If giving a dose of intra-arterial alteplase post-thrombectomy could safely improve those numbers, it could greatly increase quality of life.

It’s like Drano for your Braino…
The CHOICE study was a randomized, double-blind, placebo-controlled trial performed from December 2018 through May 2021 in 7 stroke centers in Catalonia, Spain. In this trial, the group postulated that patients who underwent successful thrombectomy (reperfusion mTICI score 2b/3) plus intra-arterial alteplase post thrombectomy (dose 0.225 mg/kg (maximum 22.5 mg) over 15 or 30 minutes) would have a greater likelihood of “excellent” neurologic outcome at 90 days. Over the study, there were 1,825 patients with acute ischemic stroke treated with thrombectomy. Of those, only 748 (41%) patients fulfilled the angiographic criteria (above), but only 121 patients were randomized, and statistics were calculated on 113 (6%). The authors looked at multiple outcome measures including:

• Primary — The proportion of patients with a score of 0 or 1 on the mRs at 90 days
• Secondary — The proportion of patients with improved angiographic findings
• Tertiary — The proportion of patients with a Barthel Scale score of 95 to 100 at day 90; the proportion of ischemic worsening (≥4-point increase on the NIHSS score) within 48 hours to 72 hours of stroke onset; and quality of life as measured with the EuroQol 5-Dimension 3-Level Self-Report Questionnaire (EQ-5D-3L) at 90 days.

The group found that within their study population receiving alteplase, 36/61 or 59.0% of patients met the primary outcome compared to 40.4% (21/52) with placebo. The adjusted risk difference within the group was 18.4% (95%CI, 0.3%-36.4%; P = .047). The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, −3.8%; 95%CI, −13.2%to 2.5%). There was no significant difference in mortality at 90 days, though there as an absolute difference favoring the alteplase group. They found no significant differences among secondary and tertiary endpoints.

The major limitation was the smaller than anticipated sample size. The group stopped enrollment early due to, “inability to maintain placebo availability and enrollment rate because of the COVID-19 pandemic.” Despite this, the treatment group exhibited a significant increase in the likelihood of mRs 0 or 1 at 90 days. While we as ED providers are not going to be dictating post-thrombectomy alteplase, this study highlights the need for additional work to classify better how we can optimize neurologic outcomes for our patients.

Source
Effect of Intra-arterial Alteplase vs Placebo Following Successful Thrombectomy on Functional Outcomes in Patients With Large Vessel Occlusion Acute Ischemic Stroke: The CHOICE Randomized Clinical Trial. JAMA. 2022 Feb 10;e221645. doi: 10.1001/jama.2022.1645. Online ahead of print.