Alteplase Impedes Progression of Poststroke Ischemic Brain Lesions

CT scan of brain
CT scan of brain
In this randomized controlled trial of IV alteplase for ischemic stroke, researchers evaluated CT or brain MRI scans before treatment and 24 to 48 hours after treatment for acute lesion visibility, extent, and swelling.

According to class II evidence presented in a meta-analysis published in Neurology, intravenous alteplase, a recombinant tissue plasminogen activator, effectively prevents or delays the progression of poststroke ischemic brain lesions on computed tomography (CT) imaging and brain magnetic resonance imaging (MRI).

Researchers reported on the findings from theThird International Stroke Trial (IST-3), a randomized controlled trial that used either intravenous alteplase at 0.9 mg/kg or control in patients with ischemic stroke (N=2916). Investigators used CT and brain MRI scans to examine patients for changes in acute lesion visibility, extent, and swelling from baseline to 24 hours and 48 hours after treatment. In addition, researchers evaluated associations between treatment randomization, changes in the appearance of brain tissue from baseline to follow-up imaging, and 6-month functional outcome. A total of 6 trials, which included the IST-3 data, were also obtained for a meta-analysis (n=4757).

Patients who experienced progression of lesion swelling (adjusted odds ratio [OR] 0.73; 95% CI, 0.66-0.79; P <.001) or lesion extent (OR 0.92; 95% CI, 0.88-0.96; P <.001) were more likely to have a worse 6-month outcome in the IST-3. In addition, patients who received alteplase had significantly lower odds of developing increased lesion visibility on follow-up imaging (OR 0.77; 95% CI, 0.67-0.89; P <.001). In the meta-analysis, treatment with alteplase was also associated with a significantly greater reduction in ischemic lesion extent compared with controls on follow-up scans (OR 0.85; 95% CI, 0.76-0.95; P =.004).

The open trial design and the lack of angiographic imaging at both baseline and follow-up represent the primary limitations of the analysis.

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Findings from this trial and the meta-analysis “indicate that early changes in the ischemic brain lesion are measurable on imaging, that these imaging appearances can predict outcome, and that treatment with alteplase limits progression of the ischemic lesion, which may in turn act as a surrogate for an improved functional outcome.”


Mair G, von Kummer R, Morris Z, et al; IST-3 Collaborative Group. Effect of IV alteplase on the ischemic brain lesion at 24-48 hours after ischemic stroke. Neurology. 2018;91(22):e2067-e2077.