Abstract
Objective: To determine any differential efficacy and safety of low- versus standard-dose intravenous alteplase for lacunar versus non-lacunar acute ischemic stroke (AIS), we performed post-hoc analyzes from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) alteplase dose-arm.
Methods: In a cohort of 3297 ENCHANTED participants, we identified those with lacunar or non-lacunar AIS with different levels of confidence (definite/probable/possible) according to pre-specified definitions based on clinical and adjudicated imaging findings. Logistic regression models were used to determine associations of lacunar AIS with 90-day outcomes (primary, modified Rankin scale [mRS] scores 2-6; secondary, other mRS scores, intracerebral hemorrhage [ICH], and early neurologic deterioration [END] or death) and treatment effects of low- versus standard-dose alteplase across lacunar and non-lacunar AIS with adjustment for baseline covariables.
Results: Of 2588 participants with available imaging and clinical data, we classified cases as definite/probable lacunar (n=490) or non-lacunar AIS (n=2098) for primary analyses. Regardless of alteplase dose received, lacunar AIS participants had favorable functional (mRS 2-6, adjusted odds ratio [95% CI] 0.60 [0.47-0.77]) and other clinical or safety outcomes, compared to participants with non-lacunar AIS. Low-dose alteplase (versus standard) had no differential effect on functional outcomes (mRS 2-6, 1.04 [0.87-1.24]) but reduced the risk of symptomatic ICH in all included participants. There were no differential treatment effects of low- versus standard-dose alteplase on all outcomes across lacunar and non-lacunar AIS (all Pinteraction ≥0.07).
Conclusions: We found no evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard-dose for definite/probable lacunar AIS.
Classification of Evidence: This study provides Class II evidence that for patients with lacunar AIS, low-dose alteplase had no additional benefit or safety over standard-dose alteplase.
Clinical Trial Registration: ENCHANTED is registered at www.clinicaltrials.gov: NCT01422616.
- Received July 6, 2020.
- Accepted in final form December 7, 2020.
- Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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