Administering the clot-busting medication alteplase directly to the site of a blocked brain artery immediately after mechanical clot removal may substantially improve functional recovery for stroke patients, according to preliminary findings from the CHOICE2 trial presented at the American Stroke Association’s International Stroke Conference 2026. The study, conducted across 14 stroke centers in Spain, indicates this two-pronged approach could address a critical gap in stroke care where more than half of survivors do not achieve full recovery even after successful artery reopening.
Large-artery ischemic strokes, which account for approximately one-quarter of all ischemic strokes, block major arteries supplying blood to significant brain areas, often resulting in death or long-term disability. While mechanical thrombectomy—the physical removal of clots—is established as a powerful treatment, its limitations are evident. "More than half of stroke survivors who have their large artery successfully cleared do not achieve full recovery 90 days later," noted study author Ángel Chamorro, M.D., Ph.D., professor of neurology at the University of Barcelona. The 2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke from the American Stroke Association, a division of the American Heart Association, recognizes thrombectomy's value but underscores the need for improved outcomes.
The CHOICE2 trial enrolled 433 adults with a median age of 76 who experienced a large-artery ischemic stroke. All participants underwent successful mechanical thrombectomy within 4.5 to 24 hours of symptom onset. They 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 the 90-day mark, the group receiving the additional medication infusion demonstrated markedly better outcomes. They were significantly more likely to achieve excellent functional recovery (57.5% versus 42.5%), representing an absolute improvement of 15 percentage points. This group also reported higher self-rated quality of life across mobility, self-care, usual activities, and lower pain and anxiety levels.
A key finding was the treatment's impact on microcirculation—the network of tiny blood vessels in the brain. Patients receiving intra-arterial alteplase were less likely to have inadequate blood flow in these small vessels (28.6% versus 50.5%), a decline of 22 percentage points. "Mechanical thrombectomy alone is often not enough to fully restore blood flow to the injured brain, even when the blocked artery appears successfully reopened," Chamorro explained. "Standard imaging can miss persistent blockages in the brain’s smallest blood vessels. Intra-arterial alteplase given after successful thrombectomy significantly increased the chances of an excellent recovery." The safety profile appeared manageable, with no significant increase in brain bleeds (1.4% versus 0.5%) or death (12.1% versus 6.4%) between the groups, though these differences require further scrutiny in larger studies.
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 agents like tenecteplase and alteplase with comparable results. However, the CHOICE2 trial represents a more robust Phase 3 investigation. The study has limitations, including its conduct primarily in Spain and reliance on non-contrast CT scans during follow-up, which may not provide detailed tissue injury data. Chamorro emphasized that while the results are "practice-informing," they are not yet "practice-changing" on their own. Broader adoption will require confirmation in additional studies, guideline review, and careful patient selection. The approach is not a universal solution but may most benefit patients with evidence of inadequate microcirculation despite large-vessel reopening.
The implications for stroke care are substantial. If future research confirms these benefits and safety, this strategy could reduce dependency on advanced imaging to identify suitable patients and offer a straightforward method to enhance recovery rates. According to the American Heart Association’s 2026 Heart Disease and Stroke Statistics, stroke remains a leading cause of death and disability, underscoring the urgent need for improved therapies. Future investigations will focus on treating the underlying causes of microcirculation disruption and validating these findings in broader populations. The abstract from this research is available in the American Stroke Association International Stroke Conference 2026 Online Program Planner. Additional context on stroke management can be found through the Association's 2026 Acute Ischemic Stroke Guideline Resources.
