Arterial thrombolysis with alteplase improves patient outcomes after successful stroke thrombectomy

This article is from the NEJM Journal Watch Review of Outcomes Improved with Intra-Arterial Alteplase After Successful Stroke Thrombectomy The early termination and small sample size of this phase 2b trial meant that a confirmatory study was warranted
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Some patients are left severely disabled by large vessel occlusive stroke, even after successful recanalization of the proximal occlusion
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Recent studies have analyzed whether bypass vein thrombolysis before stroke thrombectomy is meaningful.
In addition, researchers have also focused on whether adjuvant arterial thrombolysis after successful stroke thrombectomy can more directly resolve residual distal thrombectomy.
occlusion or microthrombosis, and improved patient outcomes
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This phase 2b trial evaluated the safety and preliminary efficacy of adjuvant arterial infusion of alteplase (0.
225 mg/kg; maximum dose 22.
5 mg) after successful stroke thrombectomy compared with infusion of placebo
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Success was initially defined as >50% to <100% reperfusion of the affected area, but protocol amendments also allowed inclusion of patients with complete reperfusion on angiography before or after stroke thrombectomy
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The study was terminated early due to slow patient recruitment and expiry of placebo, so the 121 patients randomized (1,825 patients undergoing stroke thrombectomy were screened in this study) represented approximately 60% of the planned enrollment
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Functional outcomes were significantly better in the arterial alteplase group than in the placebo group (proportion of patients with no residual symptoms and no significant disability [modified Rankin Scale score of 0 or 1], 59.
0% in the alteplase group vs.
placebo group 40.
4%)
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There were no significant between-group differences in the incidence of symptomatic intracranial hemorrhage within 24 hours and 90-day mortality
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Commentary As noted in the accompanying comments, the small sample size of this trial increases the risk of an imbalance in the characteristics of the two groups
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For example, treatment was started 40 minutes earlier in the alteplase group than in the placebo group, and in addition, the study protocol allowed investigators at each site to decide when to stop intravenous thrombolysis, which resulted in patients taking less than half the usual dose.
At least 10%, and the proportion of patients who did not reach the usual dose was even higher
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We should conduct the necessary confirmatory studies and new research on other adjunctive interventions designed to increase the benefit of stroke thrombectomy
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Reviewed article[1] Renú A et al.
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 Mar 1; 327:826; [e-pub].
(https://doi.
org/10.
1001/jama.
2022.
1645)[2] Khatri P.
Intra-arterial thrombolysis to target occlusions in distal arteries and the microcirculation.
JAMA 2022 Mar 1; 327:821; [e-pub].
(https://doi.
org/10.
1001/jama.
2021.
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