CHOICE-2 strengthens case for administering intra-arterial lytic after thrombectomy

For patients with acute ischaemic stroke caused by a large-vessel occlusion, infusing alteplase into the artery after successful endovascular thrombectomy is beneficial, conferring functional gains and reducing persistent hypoperfusion, as shown in the phase III open-label CHOICE-2 trial.

The primary outcome of a modified Rankin Scale (mRS) score of 0 or 1 at 90 days was achieved in 57.5 percent of patients who received adjunctive intra-arterial alteplase treatment vs 42.9 percent of those who underwent thrombectomy alone (adjusted risk difference, 15 percent, 95 percent confidence interval [CI], 5.7–24.3; p=0.002), reported principal investigator Dr Ángel Chamorro, professor of neurology at the University of Barcelona and head of the Comprehensive Stroke Center Hospital Clinic in Barcelona, Spain. [ISC 2026, abstract LB1]

The corresponding number needed to treat was seven patients, which is “a remarkable figure,” according to Chamorro.

Also noteworthy were the results of the CT perfusion imaging performed at 36 h from administration of the drug. Chamorro pointed out that patients who received intra-arterial treatment were less likely to have persistent hypoperfusion compared with those who underwent thrombectomy alone (29 percent vs 51 percent; p<0.001).

Finally, adjunctive intra-arterial alteplase treatment was associated with a markedly higher likelihood of achieving a Barthel index of 95–100 at 90 days among survivors (72 percent vs 62 percent; p=0.04), as well as significantly better self-reported quality of life based on the EQ-5D-5L assessment (p=0.02).

As for safety, the number of symptomatic intracerebral haemorrhage events detected at 36 h was similar between the two treatment groups (1.4 percent vs 0.5 percent; p=0.33). Ninety-day mortality rate was “very low” at 12.1 percent in the intra-arterial alteplase group and “extremely low” at 6.4 percent in the thrombectomy alone group (p=0.04), “which resulted in a significant difference in favour of [the latter],” Chamorro said.

Need for intra-arterial thrombolytics

Chamorro argued 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, microvascular hypoperfusion can persist at the tissue level, which is likely to be missed by standard imaging, he explained.

“Back in 2020, we were the first to propose that the outcome of a patient with a stroke could improve beyond angiographic success with the administration of intra-arterial alteplase, because this would hamper the damage produced by microvascular hypoperfusion,” Chamorro noted.

The results of the first CHOICE trial, reported in 2022, indeed demonstrated an 18-percent absolute increase in the proportion of patients achieving excellent functional outcome at day 90. However, the trial had to stopped early due to a placebo shortage, undermining the finality of the results. [JAMA 2022;327:826-835]

Several other trials that followed explored the effect of intra-arterial thrombolysis as an adjunct to endovascular stroke therapy. The ANGEL-TNK and PEARL yielded positive findings, whereas the POST-TNK and POST-UK trials showed no evidence of benefit. [JAMA 2025;334:582-591; JAMA 2025;334:1728-1739; JAMA 2025;333:579-588; JAMA 2025;333:589-598]

“CHOICE-2 strengthens the evidence that intra-arterial alteplase after successful thrombectomy can improve recovery in selected patients,” Chamorro said, who acknowledged that the findings are not yet practice-changing on their own.

“Broader adoption [of intra-arterial alteplase after successful thrombectomy] 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,” according to the investigator.

CHOICE-2 trial

The trial was conducted at 14 stroke centres in Spain, with blinded assessment of clinical and imaging outcomes. The trial population comprised patients with acute ischaemic stroke caused by large vessel occlusions who underwent mechanical thrombectomy within 24 h of onset and achieved successful reperfusion (expanded Thrombolysis in Cerebral Infarction grade [eTICI] 2b–3). The Alberta Stroke Program Early CT Score (ASPECTS) had to be at least 6. Those with an NIHSS score of ≥25 or higher or had contraindications to alteplase were excluded.

A total of 440 patients were randomly allocated to the adjunctive intra-arterial alteplase group or the thrombectomy alone group, with 214 (median age 77 years, 53 percent female) and 219 (median age 75 years, 49 percent female) in the respective groups included in the primary analysis. The median NIHSS score was 15, and the cause of stroke was cardioembolic in roughly half of the population. Around 64 percent of patients had a preceding intravenous thrombolysis.