Administering the clot-busting medication alteplase directly into a brain artery after mechanical clot removal may significantly improve recovery outcomes for patients experiencing large-artery ischemic strokes, according to preliminary research presented at the American Stroke Association's International Stroke Conference 2026. The CHOICE2 trial, conducted across 14 stroke centers in Spain, indicates this combined approach could help more patients achieve excellent functional recovery following these severe strokes.
Large-artery ischemic strokes, which account for approximately one-quarter of all ischemic strokes, block major arteries supplying blood to significant brain areas, often causing death or long-term disability. While mechanical thrombectomy—the physical removal of clots from blocked brain arteries—represents a powerful treatment, more than half of patients who undergo successful clot removal do not achieve full recovery within 90 days. The American Heart Association's 2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke recognizes thrombectomy's effectiveness but highlights the ongoing need for improved outcomes.
The CHOICE2 trial involved 433 adults with a median age of 76 who experienced large-artery ischemic strokes and were treated within 4.5 to 24 hours of symptom onset. All participants underwent successful mechanical thrombectomy, with 214 randomly assigned to receive an additional 15-minute infusion of alteplase directly into the affected brain artery, while 219 received thrombectomy alone. At 90 days post-treatment, patients receiving the combined therapy demonstrated significantly better outcomes: 57.5% achieved excellent functional recovery compared to 42.5% in the thrombectomy-only group, representing a 15 percentage point absolute improvement.
Study author Ángel Chamorro, M.D., Ph.D., professor of neurology at the University of Barcelona, explained that mechanical thrombectomy alone often fails to fully restore blood flow to injured brain tissue, even when the main artery appears successfully reopened. "Standard imaging can miss persistent blockages in the brain's smallest blood vessels," Chamorro noted. "Intra-arterial alteplase given after successful thrombectomy significantly increased the chances of an excellent recovery." The combined treatment group also showed reduced incidence of inadequate blood flow in small brain vessels (28.6% versus 50.5%), better self-reported quality of life across multiple domains, and no significant increase in brain bleeding or mortality rates.
These findings build upon earlier research, including the initial CHOICE trial published in 2022, which showed similar benefits but was limited by small participant numbers and early termination due to the COVID-19 pandemic. Other studies like the ANGEL-TNK and PEARL trials using different clot-dissolving agents have reported comparable results. The American Stroke Association provides additional resources through their stroke.org website, where stroke remains a leading cause of death and serious disability globally.
Despite promising results, researchers emphasize that CHOICE2 findings are preliminary and require confirmation through additional studies before becoming standard practice. The trial's limitations include its reliance on non-contrast CT scanning during follow-up, which reflects real-world clinical practice but may not provide detailed information about brain tissue injury and recovery. Although conducted in Spain, participants came from 20 countries across three continents, suggesting results may be generalizable to diverse populations.
"These results are practice-informing but not yet practice-changing on their own," Chamorro stated. "While CHOICE2 strengthens the evidence that intra-arterial alteplase given after successful thrombectomy can improve recovery, broader adoption will require confirmation in additional studies, guideline review and careful consideration of patient selection." Future research will focus on treating underlying causes of disrupted blood flow in the brain's microcirculation and determining which patients benefit most from this combined approach. If confirmed, this strategy could eventually reduce reliance on advanced imaging techniques to identify patients with persistent perfusion abnormalities who would benefit from additional clot-busting medication after thrombectomy.
