Can MRI-guided thrombolysis with alteplase improve outcomes in stroke patients with unknown time of onset?
MRI-guided thrombolysis using intravenous alteplase resulted in better functional outcomes in acute stroke patients with an unknown time of onset, according to a study in the Aug. 16 issue of the New England Journal of Medicine.
Intravenous thrombolysis with alteplase is the standard treatment for acute ischemic stroke, but it's only recommended for patients within 4.5 hours of symptom onset, wrote lead author Götz Thomalla, MD, and colleagues. But that time is unknown in 27 percent of strokes, they added.
Researchers created the WAKE-UP trial to determine if alteplase treatment, with a mismatch between diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR), would improve functional outcomes in those with unknown onset times.
Thomalla and colleagues randomized 503 patients to receive either alteplase or placebo. The primary endpoint was a favorable outcome at 90 days, defined by a score of 0 or 1 on a modified Rankin scale of neurologic disability, with 0 indicating no symptoms and 6 meaning death.
In the alteplase group, 53 percent of patients achieved a favorable outcome at 90 days. In the placebo group that mark was 42 percent. The alteplase group included 10 deaths, compared to three in the placebo cohort.
The median Rankin scores were 1 and 2 for the alteplase and placebo group, respectively.
“In patients with acute stroke with an unknown time of onset, intravenous alteplase guided by a mismatch between diffusion-weighted imaging and FLAIR in the region of ischemia resulted in a significantly better functional outcome and numerically more intracranial hemorrhages than placebo at 90 days,” the authors concluded.
In a related editorial, Tudor G. Jovin, MD, argued the results of the WAKE-UP trial could not answer two important questions: Do the MRI findings provide adequate evidence for the modality as a stand-alone prerequisite for thrombectomy? Should these patients be treated with intravenous alteplase prior to thrombectomy?
Jovin argued most endovascular centers us CT perfusion as the first-line imaging of choice, which was not included in the study. Additionally, thrombectomy patients were excluded in the trial, which he suggests is a primary reason these questions cannot be answered.
“Although the findings of the WAKE-UP trial provide reason for optimism, many questions remain,” Jovin wrote. “It is important that clinical equipoise be maintained so that confirmatory trials can be performed. If the results of such trials are positive, they would expand the population of patients with acute stroke who are eligible for intravenous thrombolysis.”
Matt joined Chicago’s TriMed team in 2018 covering all areas of health imaging after two years reporting on the hospital field. He holds a bachelor’s in English from UIC, and enjoys a good cup of coffee and an interesting documentary.