Thrombolysis with alteplase improves functional outcome in stroke patients with unknown time of onset
MRI-guided thrombolysis using intravenous alteplase could be the key to better functional outcomes in acute stroke patients whose time of onset is unknown, researchers wrote in the New England Journal of Medicine this week.
Intravenous thrombolysis with alteplase is the standard of care when it comes to acute stroke, Gotz Thomalla, MD, and colleagues said in NEJM—but it’s only recommended to patients within four and a half hours of a stroke. That covers the majority of ischemic stroke cases but neglects the up to 27 percent of patients whose time of onset is unknown.
“Such patients are generally excluded from treatment with intravenous alteplase, and only some of them are candidates for mechanical thrombectomy,” Thomalla and co-authors wrote.
In many cases, they said, those patients are ones whose stroke onset during sleep, likely within three hours of getting up. The team designed the aptly named WAKE-UP trial to determine if treatment with alteplase, with a mismatch between diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR), would improve functional outcomes in patients with an unknown time of stroke onset.
The study was built off previous research, which proved the efficacy of MRI and FLAIR in predicting symptom onset within four and a half hours before imaging in patients with known stroke onset, the authors said. Visible ischemic lesions on diffusion-weighted imaging were indicators of onset in MRI, and, combined with a clearly visible hyperintense signal in the same region in FLAIR, the pair predicted stroke.
In Thomalla et al.’s trial, 503 patients with an unknown time of stroke onset were randomized to receive either intravenous alteplase or placebo. Just over half of the group met the primary endpoint of a favorable outcome, the researchers reported, though the alteplase cohort saw 10 deaths compared with the placebo’s 4. Rate of symptomatic intracranial hemorrhage also reached 2 percent in those treated with alteplase, while it stayed around 0.4 percent in patients treated with placebo.
The results suggest treatment with intravenous alteplase could lead to better functional outcomes in a stroke cohort with unknown onset time, the researchers said.
“Among patients with acute stroke and an unknown time of symptom onset who had MRI findings of an ischemic lesion on diffusion-weighted imaging but no parenchymal hyperintensity in the corresponding region on FLAIR, intravenous thrombolysis with alteplase resulted in a better functional outcome than treatment with placebo,” the authors wrote. “Intravenous alteplase was associated with numerically better scores on the modified Rankin scale and with a shift toward better outcomes in all categories.”
After graduating from Indiana University-Bloomington with a bachelor’s in journalism, Anicka joined TriMed’s Chicago team in 2017 covering cardiology. Close to her heart is long-form journalism, Pilot G-2 pens, dark chocolate and her dog Harper Lee.