Low- versus standard-dose alteplase in acute lacunar ischemic stroke: the ENCHANTED trial - online supplemental

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.