Low-dose alteplase has no advantage over the standard dose for definitive / probable lacunar AIS

Low-dose alteplase does not appear to offer any benefit over standard-dose alteplase in the management of specific or probable acute lacunar ischemic stroke, a study in Neurology suggests.

The study was an analysis of an alteplase treatment cohort from the Enhanced Control of Hypertension and Thrombolysis Stroke Study ( Identifier: NCT01422616) that included patients with lacunar and non-lacunar acute ischemic stroke (AIS) data. Study researchers classified patients as patients with definite / likely lacunar (n = 490) or non-lacunar AIS (n = 2098).

The researchers in this analysis used logistic regression models to examine associations of lacunar AIS with 90-day results. The primary outcome was a composite endpoint for disability or death as defined by Modified Rankin Scale (mRS) from 2 to 6 90 days after randomization. Secondary outcomes included severe disability or death (mRS score, 3-6), intracerebral hemorrhage (ICH), and early neurological deterioration (END) or death. The treatment effects of alteplase compared to the standard dose of alteplase were also investigated in patients with lacunar and non-lacunar AIS.

Patients with lacunar AIS had favorable functional results across all alteplase doses compared to patients with non-lacunar AIS (adjusted odds ratio) [OR]0.60; 95% CI, 0.47-0.77; P <0.001). In addition, patients with lacunar AIS also had more favorable outcomes when defined by death alone (adjusted OR 0.13; 95% CI 0.04-0.43; P <0.001).

While low-dose alteplase had no advantage over the standard dose in functional results (adjusted OR 1.04; 95% CI 0.87-1.24), the former reduced the risk of symptomatic intracranial bleeding in all patients. There was also no difference in the treatment effect of low-dose alteplase in the standard dose on any of the other endpoints in patients with lacunar and non-lacunar AIS (all pinteraction ≥.07).

The limitations of this study included insufficient statistical power, inevitable selection biases and the inclusion of a cohort of clinical studies in which predominantly Asian patients with mild to moderate stroke participated.

The study researchers concluded: “Patients with lacunar AIS should receive standard dose intravenous alteplase according to the standard eligibility criteria as with other AIS subtypes.”


Zhou Z., Delcourt C., Xia C. et al. Low- or Standard-Dose Alteplase in Acute Lacunar Ischemic Stroke: The ENCHANTED Study. Neurology. Published online February 3, 2021. doi: 10.1212 / WNL.0000000000011598

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