Intra-arterial Alteplase After Thrombectomy Shows Significant Improvement in Stroke Recovery Outcomes

The phase 3 CHOICE2 trial has demonstrated that administering intra-arterial alteplase following successful mechanical thrombectomy significantly improves functional outcomes in patients with large-vessel occlusion acute ischemic stroke. The findings, presented as late-breaking data at the 2026 International Stroke Conference in New Orleans, represent a potential advancement in stroke treatment for patients who undergo successful clot removal but still face suboptimal recovery rates.

Trial Design and Patient Population

The investigator-initiated, multicenter, open-label, randomized trial enrolled 440 patients across 14 stroke centers in Spain, with 431 included in the modified full analysis set. Participants had a median age of 76 years, with women comprising 51% of the cohort and 95% being white. All participants had acute ischemic stroke due to large-vessel occlusion and achieved successful reperfusion (eTICI 2b50–3) after endovascular treatment.

Patients were randomized to receive either endovascular treatment alone (217 patients) or endovascular treatment followed by adjunctive intra-arterial thrombolysis with alteplase (214 patients). Randomization occurred within 4.5 hours of last known well, or between 4.5 and 24 hours when multimodal imaging demonstrated salvageable tissue. The alteplase dose was 0.225 mg/kg (maximum 20 mg), infused directly into the affected artery over 15 minutes.

Primary Outcomes Show Significant Improvement

The trial's primary outcome was functional status at 90 days, measured by the modified Rankin Scale (mRS). Patients receiving the combination therapy achieved excellent functional outcomes (mRS 0-1) at a rate of 57.5% compared to 42.5% for those receiving thrombectomy alone, representing a 15% adjusted risk difference (95% CI, 5.7%-24.3%; P = .002).

"Mechanical thrombectomy alone is often not enough to fully restore blood flow to the injured brain, even when the blocked artery appears successfully reopened," said Ángel Chamorro, M.D., Ph.D., professor of neurology at the University of Barcelona and head of the Comprehensive Stroke Center Hospital Clinic in Barcelona. "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."

Microvascular Perfusion Benefits

Key secondary outcomes revealed substantial improvements in microvascular perfusion. Patients who received adjunctive alteplase were significantly less likely to have inadequate blood flow in small vessels based on imaging compared with the thrombectomy-alone group (28.6% vs 50.5%, respectively), with an adjusted risk difference of −22% (−31.5% to −12.4%; P < .001).

The combination therapy group also demonstrated superior quality of life measures, with patients rating themselves higher in mobility, self-care, performing usual activities, and reporting lower pain/discomfort and depression/anxiety scores.

Safety Profile Remains Acceptable

Safety analysis showed that patients receiving alteplase were not significantly more likely to experience brain bleeding (1.4% vs 0.5%; P = .33). However, there was a significantly higher likelihood of mortality in the treatment versus control group (12.1% vs 6.4%; P = .04). According to Chamorro, the apparent difference in mortality is likely due to a low event rate in the control group.

Clinical Context and Future Implications

Large-artery ischemic strokes account for approximately one in four ischemic strokes and can cause significant death and long-term disability due to blockage of large arteries supplying blood to substantial brain areas. Despite successful thrombectomy, more than half of stroke survivors do not achieve full recovery 90 days after treatment.

The CHOICE2 results build upon favorable preliminary findings from the earlier CHOICE trial, which was published in 2022 but included a smaller patient population (121 patients) and was halted early due to the COVID-19 pandemic's interference with patient recruitment and placebo supply.

Measured Approach to Implementation

"These results are practice-informing but not yet practice-changing on their own," Chamorro emphasized. "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."

The researchers noted that this approach should not be viewed as a "one-size-fits-all" treatment. It is most likely to benefit patients who, despite large-vessel reopening, have evidence of inadequate blood flow in their microcirculation. If future studies and meta-analyses confirm the safety of this strategy, it may eventually reduce the need to rely on advanced imaging techniques to identify patients with persistent perfusion abnormalities appropriate for this treatment.

Study Limitations and Generalizability

The study's limitations include the requirement for 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. However, although the study was conducted only in Spain, participants were from 20 countries across three continents, suggesting the results should be generalizable to many populations.

Future research will focus on confirming the CHOICE2 findings and developing ways to treat the underlying causes leading to disruption of blood flow in the microcirculation.