Thrombolysis Works Early Enough for Lacunar Strokes

Stroke patients with lacunar infarcts may also benefit from pharmacological reperfusion with alteplase, according to a post hoc analysis of the WAKE-UP trial.

A favorable outcome at 90 days was numerically more likely when these patients were randomized to alteplase rather than placebo (59% vs 46%, adjusted OR 1.68, 95% CI 0.76-3.69). The distribution of modified Rankin Scale scores also non-significantly shifted to favor the alteplase group by then (adjusted OR 1.94, 95% CI 0.95-3.93).

“While the WAKE-UP trial was not powered to demonstrate the efficacy of treatment in subgroups of patients, the results indicate that the association of IV alteplase with functional outcome does not differ in patients with imaging-defined lacunar infarcts compared with those experiencing other stroke subtypes,” wrote Ewgenia Barow, MD, of the University Medical Center Hamburg-Eppendorf Martinistraße in Germany, and colleagues in JAMA Neurology.

Whether thrombosis plays a role in the pathophysiology of lacunar infarctions has been uncertain, clot-dissolving treatment is of questionable help, the investigators noted. Arguments against using alteplase in these patients include concerns about an increased risk of symptomatic intracranial hemorrhage (SICH) and the idea that lacunar strokes are associated with a “more benign” natural history, they added.

Indeed, one death and one SICH were observed within 90 days of alteplase administration, whereas no such events occurred in the placebo group.

The one SICH patient had not been treated for hypertension (with systolic blood pressure reaching 250 mm Hg) on admission nor during infusion. “This patient has to be considered a protocol violation and should not have been treated with IV alteplase owing to uncontrollable hypertension,” Barow and colleagues argued.

“The current analysis further tips the scales strongly in favor of treating lacunar strokes.While post hoc, exploratory, and likely underpowered, the study by Barow and colleagues shows no effect modification by stroke subtype,” commented Pooja Khatri, MD, of the University of Cincinnati, in an accompanying editorial.

WAKE-UP was a trial of MRI-guided thrombolysis in patients with acute strokes of unknown onset time. Out of the 503 patients enrolled, 108 had acute lacunar infarcts (subcortical ischemic lesions in the territory of a small penetrating artery).

This group was younger than the rest of the WAKE-UP cohort (average age 63 vs 66, P=0.003) and had more men (68.5% vs 63.5%). They were admitted with less severe strokes (NIH Stroke Scale score median 5 vs 6 points, P<0.001) and were less likely to have a history of atrial fibrillation (1.9% vs 14.4%, P<0.001). Lesions were smaller as well (median DWI lesion volume 0.7 vs 3.8 mL, P<0.001).

Within the lacunar infarct subgroup, there were no significant baseline differences between the 50.9% receiving alteplase and the rest assigned to placebo.

Given the new signal that thrombolysis can work in lacunar infarction, it may be logistically harder to select stroke patients for this therapy more than 4.5 hours from last known well, Khatri said.

“The hope has been that we can replace MRI by [one or two] CT imaging strategies as a more cost-effective strategy for identifying these patients, but this now seems more distant,” the editorialist wrote. “Emergency departments that have a policy of using CT imaging first will have to take many patients without occlusions visualized on CT angiography to the MRI scanner expeditiously, to avoid missing patients with lacunar infarcts.”

It may be that MRI is “the most inclusive and efficient approach for the largest proportion of patients,” she stated.

last updated 03.25.2019