The administration of the clot-busting medication alteplase directly into a brain artery immediately after successful mechanical clot removal may substantially improve recovery for patients suffering large-artery ischemic strokes, according to preliminary findings from the CHOICE2 trial presented at the American Stroke Association's International Stroke Conference 2026. This two-pronged approach addresses a critical limitation in current stroke care where more than half of patients whose large arteries are successfully reopened still fail to achieve full recovery within 90 days.
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—remains a powerful treatment per the American Stroke Association's 2026 guidelines, study author Ángel Chamorro, M.D., Ph.D., notes that "mechanical thrombectomy alone is often not enough to fully restore blood flow to the injured brain, even when the blocked artery appears successfully reopened." Standard imaging techniques frequently miss persistent blockages in the brain's smallest blood vessels, a problem this combined approach aims to mitigate.
The CHOICE2 trial involved 433 adults treated at 14 Spanish stroke centers between December 2023 and August 2025. All participants experienced large-artery ischemic strokes and underwent successful mechanical thrombectomy within 4.5 to 24 hours of symptom onset. Patients were then randomized to receive either standard post-thrombectomy care (219 patients) or standard care plus a 15-minute infusion of alteplase directly into the affected brain artery (214 patients).
At 90-day follow-up, the group receiving combined treatment demonstrated significantly better outcomes. They were 15 percentage points more likely to achieve excellent functional recovery (57.5% versus 42.5%) and 22 percentage points less likely to show inadequate blood flow in small brain vessels on imaging (28.6% versus 50.5%). These patients also reported higher quality of life across multiple domains including mobility, self-care, usual activities, and lower pain and anxiety levels. Importantly, the combined approach did not significantly increase the risk of brain bleeding (1.4% versus 0.5%) or death (12.1% versus 6.4%).
These findings build upon earlier research, including the initial CHOICE trial published in 2022 and similar studies like the ANGEL-TNK and PEARL trials, which used different clot-dissolving agents with comparable results. The American Heart Association's 2026 Heart Disease and Stroke Statistics highlight the ongoing urgency of improving stroke outcomes, as stroke remains the fourth leading cause of death in the United States.
While promising, Chamorro cautions that these "results are practice-informing but not yet practice-changing on their own." 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 tissue recovery information. Although conducted in Spain, participants came from 20 countries across three continents, suggesting findings may be generalizable to diverse populations.
Future research will need to confirm these results through additional studies and meta-analyses before broader clinical adoption. As Chamorro explains, "broader adoption will require confirmation in additional studies, guideline review and careful consideration of patient selection." The approach appears most beneficial for patients with evidence of inadequate microcirculation despite large-vessel reopening, and if proven safe in further research, could eventually reduce reliance on advanced imaging to identify candidates. Researchers will also investigate underlying causes of microcirculation disruption to develop more targeted treatments.
