Giving alteplase after clot removal may improve recovery in large-artery ischaemic stroke, a Spanish trial has found.
Large-artery ischaemic strokes, caused by blood clots, account for about one in four ischaemic strokes.
They can lead to death and long-term disability by blocking major brain arteries.
Removing clots directly from blocked brain arteries, a procedure called thrombectomy, is used for major strokes due to large-vessel blockages in select patients.
However, more than half of survivors whose large artery is successfully cleared do not fully recover by 90 days.
Ángel Chamorro is professor of neurology at the University of Barcelona and head of the Comprehensive Stroke Center Hospital Clinic in Barcelona.
Chamorro said: “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 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.”
In the CHOICE2 trial, more than 400 adults with large-artery ischaemic stroke were treated in Spain within 4.5 to 24 hours of first symptoms, allowing clot removal and optional alteplase delivered to the same site immediately after.
Patients were randomised to thrombectomy alone (219 people) or thrombectomy plus intra-arterial alteplase (214 people).
At 90 days, those given alteplase after clot removal were more likely to achieve excellent functional outcome, 57.5 per cent versus 42.5 per cent, an absolute gain of 15 percentage points.
They were less likely to show inadequate small-vessel blood flow on imaging, 28.6 per cent versus 50.5 per cent, a decline of 22 percentage points.
Quality-of-life ratings improved across mobility, self-care, usual activities, pain or discomfort, and anxiety or depression.
Rates of brain bleed were not significantly different, 1.4 per cent versus 0.5 per cent, nor death, 12.1 per cent versus 6.4 per cent.
An earlier study, CHOICE, reported in 2022, also suggested better outcomes with alteplase plus thrombectomy, though it was small at 121 patients and halted early during the COVID-19 pandemic.
Chamorro said: “These results are practice-informing but not yet practice-changing on their own.
“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.
“Importantly, 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.
“However, 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.”
Participants were 433 adults, median age 76 years; 51 per cent were women and 95 per cent were white, treated at 14 centres in Spain between December 2023 and August 2025.
All underwent mechanical thrombectomy with successful arterial reperfusion. None had serious neurological problems before stroke, and none had a very severe stroke by standard scales.
A limitation was reliance on non-contrast CT during follow-up, which mirrors practice but gives less detail on tissue injury and recovery.
Although run in Spain, participants came from 20 countries across three continents.
