Low- versus standard-dose alteplase in acute lacunar ischemic stroke: The ENCHANTED Trial Link to paper on Neurology. Authors 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 Abstract Objective: To determine any differential efficacy & 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 & 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 & 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], & early neurologic deterioration [END] or death) & treatment effects of low- versus standard-dose alteplase across lacunar & non-lacunar AIS with adjustment for baseline covariables. Results: Of 2588 participants with available imaging & 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]) & 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 & 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. Keywords All Clinical Neurology All Clinical trials CT Infarction MRI Related links Link to paper on Neurology Professor Joanna Wardlaw Dr Grant Mair Brain & nervous system Stroke ENCHANTED Social media tags & titles Featured paper: Low- versus standard-dose alteplase in acute lacunar ischemic stroke: The ENCHANTED Trial @EdinUniBrainSci @GreenJournal Publication date 10 Feb, 2021