Low-Dose vs Standard-Dose Alteplase in Acute Lacunar Ischemic Stroke: The ENCHANTED Trial.

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

doi:10.1212/wnl.0000000000011598

Abstract

ObjectiveTo 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.MethodsIn 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.ResultsOf 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).ConclusionsWe 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.Clinical Trial RegistrationClinicaltrials.gov identifier NCT01422616.

Highlights

In a cohort of 3,297 ENCHANTED participants, we identified those with lacunar or nonlacunar acute ischemic stroke (AIS) with different levels of confidence
We found no evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard dose for definite/ probable lacunar AIS
Patients with lacunar acute ischemic stroke (AIS) are eligible to receive IV thrombolysis, given comparable favorable outcomes to other common AIS pathologic subtypes.[1,2,3]. These results were confirmed in a recent subgroup analysis of the Efficacy and Safety of Magnetic Resonance Imaging–Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial, where the safety and efficacy of standard-dose IV alteplase were comparable between lacunar and nonlacunar subtypes defined on baseline MRI.[4]

Summary

Introduction

In a cohort of 3,297 ENCHANTED participants, we identified those with lacunar or nonlacunar AIS with different levels of confidence 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 covariable

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Results

Discussion

Conclusion