Low-dose vs standard-dose alteplase in acute lacunar ischemic stroke: the ENCHANTED trial

Zien Zhou, Candice Delcourt, Chao Xia, Sohei Yoshimura, Cheryl Carcel, Takako Torii-Yoshimura, Shoujiang You, Alejandra Malavera, Xiaoying Chen, Maree L. Hackett, Mark Woodward, John Chalmers, Jianrong Xu, Thompson G. Robinson, Mark W. Parsons, Andrew M. Demchuk, Richard I. Lindley, Grant Mair, Joanna M. Wardlaw, Craig S. Anderson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)
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Abstract

Objective: To determine any differential efficacy and safety of low- vs standard-dose IV alteplase for lacunar vs nonlacunar 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 3,297 ENCHANTED participants, we identified those with lacunar or nonlacunar AIS with different levels of confidence (definite/according to prespecified 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 or death) and treatment effects of low- vs standard-dose alteplase across lacunar and nonlacunar AIS with adjustment for baseline covariables. Results: Of 2,588 participants with available imaging and clinical data, we classified cases as definite/probable lacunar (n = 490) or nonlacunar AIS (n = 2,098) for primary analyses. Regardless of alteplase dose received, lacunar AIS participants had favorable functional (mRS 2-6, adjusted odds ratio [95% confidence interval] 0.60 [0.47-0.77]) and other clinical or safety outcomes compared to participants with nonlacunar 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- vs standard-dose alteplase on all outcomes across lacunar and nonlacunar AIS (all pinteraction ≥0.07). Conclusion: sWe found no evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard dose for definite/probable lacunar AIS.Classification of EvidenceThis study provides Class II evidence that for patients with lacunar AIS, low-dose alteplase had no additional benefit or safety over standard-dose alteplase.

Original languageEnglish
Pages (from-to)e1512-e1526
Number of pages15
JournalNeurology
Volume96
Issue number11
Early online date3 Feb 2021
DOIs
Publication statusPublished - 16 Mar 2021
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

A correction exists for this article and can be found in Neurology (2021) Vol 97(10) p. 512 at doi: 10.1212/WNL.0000000000012302

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