Patients with minor nondisabling acute ischemic stroke who were treated with alteplase vs. aspirin did not experience an increased likelihood of favorable functional outcome after 90 days, according to findings recently published in JAMA.
“Although alteplase is the standard of care for patients with ischemic stroke and disabling deficits regardless of severity judged by [National Institutes of Health Stroke Scale] scores, the optimal management of patients with not clearly disabling deficits is unclear,” Pooja Khatri, MD, director of the Acute Stroke Program for the University of Cincinnati Stroke Team, and colleagues wrote. “Most major trials of alteplase explicitly excluded varying subsets of patients with the mildest deficits. The IST 3 trial permitted enrollment of patients with minor deficits, but only when the local enrolling physician had personal equipoise regarding benefit and without collecting data to distinguish which enrolled patients had disabling vs. nondisabling deficits at presentation.”
Researchers conducted a phase 3b, randomized, double-blind clinical trial of 313 patients, out of a planned 948, enrolled at 53 stroke networks to test the efficacy and safety of alteplase administered within 3 hours of onset of ischemic stroke symptoms. The patients were randomized, with 156 receiving standard dose (0.9 mg/kg) of IV alteplase with oral placebo and 157 receiving oral aspirin 325 mg, with IV placebo.
Researchers found that 78.2% of patients receiving alteplase showed favorable functioning outcomes at 90 days compared with 81.5% of those receiving aspirin. Researchers also found that 3.2% of alteplase-treated patients had symptomatic intracranial hemorrhage, defined as any neurologic decline within 36 hours attributed to intracranial hemorrhage by local investigators. No patients treated with aspirin had symptomatic intracranial hemorrhage. The study was ended earlier than planned due to low patient enrollment.
“Although the study did not demonstrate a significant benefit of alteplase for patients with minor nondisabling acute ischemic stroke, the very early study termination precludes any definitive conclusions,” Khatri and colleagues wrote.
In an accompanying editorial, William J. Powers, MD, from the University of North Carolina’s department of neurology, discussed the premature termination of the trial which resulted in a lower sample size that kept the favorable outcome scores so similar.
“The findings from the report by Khatri et al provide more certain, but not definitive, evidence suggesting that IV alteplase appears unlikely to meaningfully improve functional outcome in patients with mild ischemic stroke with initial [National Institutes of Health Stroke Scale] scored of five or lower and with nondisabling deficits, and that for these patients, treatment with aspirin along with close monitoring may be an appropriate course of action,” Powers said.– by Jake Scott
Khatri reports payment to her university department for research efforts from Genentech (lead PI of PRISMS), Neurospring (coinvestigator; CREATE grant), Lumosa (data and safety monitoring board and consultant), Cerenovus (Investigators-initiated study, ENDO LOW PI) and the National Institutes of Health/National Institute of Neurological Disorders and Stroke. Please see the full study for a list of all authors’ relevant financial disclosures.