Preliminary results from the CHOICE2 trial indicate that delivering the clot-busting medication alteplase directly into the affected brain artery after successful mechanical thrombectomy may substantially improve recovery outcomes for patients experiencing large-artery ischemic strokes. The research, presented at the American Stroke Association's International Stroke Conference 2026, builds on earlier findings and could influence future stroke treatment protocols for this serious condition that accounts for approximately one-quarter of all ischemic strokes.
Large-artery ischemic strokes block major arteries supplying blood to significant brain areas, often resulting in death or long-term disability. While mechanical thrombectomy has become a standard treatment for eligible patients, more than half of survivors whose large arteries are successfully cleared do not achieve full recovery within 90 days. According to study author Ángel Chamorro, M.D., Ph.D., professor of neurology at the University of Barcelona, "Mechanical thrombectomy alone is often not enough to fully restore blood flow to the injured brain, even when the blocked artery appears successfully reopened."
The Phase 3 CHOICE2 trial involved 433 adults treated at 14 stroke centers in Spain between December 2023 and August 2025. All participants had experienced ischemic strokes in large brain arteries and underwent successful mechanical thrombectomy within 4.5 to 24 hours of symptom onset. Patients were randomized to receive either standard clot removal (219 patients) or clot removal plus a 15-minute infusion of alteplase directly into the affected artery (214 patients).
At 90 days post-treatment, those receiving the combined approach demonstrated significantly better outcomes. They were 15 percentage points more likely to achieve excellent functional recovery (57.5% versus 42.5%), showed a 22 percentage point reduction in inadequate blood flow in small brain vessels (28.6% versus 50.5%), and reported higher quality of life across multiple domains including mobility, self-care, and reduced pain/discomfort. The treatment did not significantly increase brain bleeding risk (1.4% versus 0.5%) or mortality (12.1% versus 6.4%).
These findings align with earlier research, including the 2022 CHOICE trial and similar studies like ANGEL-TNK and PEARL, though CHOICE2 represents a larger, more robust investigation. The earlier CHOICE study, published in 2022, was halted prematurely due to COVID-19 pandemic disruptions and involved only 121 patients. The American Stroke Association's 2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke currently recognizes thrombectomy as a powerful treatment for major strokes caused by large-vessel blockages in select patients.
Despite promising results, researchers emphasize that these findings are practice-informing rather than practice-changing at this stage. Chamorro noted that broader adoption will require confirmation in additional studies, guideline review, and careful patient selection. "This approach should not be viewed as a 'one-size-fits-all' treatment," he explained. "It is most likely to benefit patients who, despite large-vessel reopening, have evidence of inadequate blood flow in their microcirculation."
The study has limitations, including its reliance on non-contrast CT scanning during follow-up, which reflects real-world 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. Future research will focus on treating underlying causes of microcirculation disruption and confirming CHOICE2 findings through additional studies and meta-analyses.
According to the American Heart Association's 2026 Heart Disease and Stroke Statistics, stroke remains the fourth leading cause of death in the United States. The potential for improved recovery through combined thrombectomy and intra-arterial alteplase treatment could have significant implications for reducing long-term disability and healthcare costs associated with stroke care. As research continues to evolve, this approach may eventually reduce reliance on advanced imaging techniques to identify patients with persistent perfusion abnormalities who would benefit most from this treatment strategy.
