Low-Dose Alteplase Has No Advantage Over Standard Dose for Definite/Probable Lacunar AIS

Doctor examination for diagnosis disease
This trial compared the efficacy and safety of low- and standard-dose alteplase for the treatment of lacunar acute ischemic stroke.

Low-dose alteplase does not appear to provide any advantages over standard-dose alteplase in the treatment of definite or probable acute lacunar ischemic stroke, a study in Neurology suggests.

The study was an analysis of an alteplase treatment cohort from the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) trial (ClinicalTrials.gov Identifier: NCT01422616), including patients with lacunar and nonlacunar acute ischemic stroke (AIS) based on imaging and clinical data. Study researchers classified patients as having definite/probable lacunar (n=490) or nonlacunar AIS (n=2098).

The investigators of this analysis used logistic regression models to examine associations of lacunar AIS with 90-day outcomes. The primary outcome was a composite endpoint of disability or death, as defined by modified Rankin scale (mRS) scores of 2 to 6, at 90 days following randomization. Secondary outcomes included major disability or death (mRS score, 3-6), intracerebral hemorrhage (ICH), and early neurologic deterioration (END) or death. Treatment effects of low- compared with standard-dose alteplase were also examined across patients with lacunar and nonlacunar AIS.

Patients with lacunar AIS had favorable function outcomes across all alteplase doses compared with patients with nonlacunar AIS (adjusted odds ratio [OR], 0.60; 95% CI, 0.47-0.77; P <.001). In addition, patients with lacunar AIS also had more favorable outcomes even when defined by death alone (adjusted OR, 0.13; 95% CI, 0.04-0.43; P <.001).

While low-dose alteplase had no advantage over standard dosing on functional outcomes (adjusted OR, 1.04; 95% CI, 0.87-1.24), the former reduced the risk of symptomatic intracranial hemorrhage in all patients. There was also no differential treatment effect of low-dose compared with standard-dose alteplase on all other outcomes across patients with lacunar and nonlacunar AIS (all Pinteraction ≥.07).

Limitations of this study included insufficient statistical power, inevitable selection bias, and the inclusion of a clinical trial cohort that predominantly comprised Asian patients with mild-to-moderate stroke.

The study researchers concluded, “According to standard eligibility criteria, patients with lacunar AIS should receive standard dose intravenous alteplase as with other AIS subtypes.”


Zhou Z, Delcourt C, Xia C, et al. Low- versus standard-dose alteplase in acute lacunar ischemic stroke: The ENCHANTED trial. Neurology. Published online February 3, 2021. doi:10.1212/WNL.0000000000011598