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TOPLINE:

Adjunctive intra-arterial alteplase after successful thrombectomy for acute ischemic stroke due to large vessel occlusion (LVO) was linked to a higher rate of excellent functional outcome at 90 days than thrombectomy alone, a new trial showed. However, the findings, first reported by Medscape Medical News at the International Stroke Conference, 2026, also revealed a higher mortality rate at 90 days with adjunctive intra-arterial alteplase.

METHODOLOGY:

• Researchers conducted a randomized, open-label trial with blinded outcome assessments at 14 stroke centers in Spain from 2023 to 2025, enrolling 433 adults (median age, 76 years; 51% women) with acute ischemic stroke due to LVO. Patients underwent successful thrombectomy with an expanded Treatment in Cerebral Ischemia score of 2b50 to 3 and were enrolled within 4.5 hours of last known well with an Alberta Stroke Program Early CT Score ≥ 6 or enrolled within 24 hours if advanced imaging showed salvageable tissue.
• Participants were randomly assigned to undergo thrombectomy alone (control group; n = 219) or thrombectomy with intra-arterial alteplase at 0.225 mg/kg (maximum dose, 20 mg/kg) infused over 15 minutes (intervention group; n = 214).
• The primary outcome was excellent functional outcome at 90 days, defined as having a modified Rankin Scale score of 0 or 1. Secondary outcomes included residual hypoperfusion on follow-up CT perfusion and between-group difference in the volume of hypoperfusion.
• Safety outcomes included symptomatic intracranial hemorrhage at 36 hours, any intracranial hemorrhage, serious adverse events, and all-cause mortality at 90 days.

TAKEAWAY:

• At 90 days, 57.5% of patients in the intervention group achieved excellent functional outcome compared with 42.5% of those in the control group (adjusted risk difference, 15.0%; P = .002).
• Residual hypoperfusion on follow-up CT perfusion occurred in 29% of intervention patients vs 50.5% of control individuals (adjusted risk difference, -22.0%; P < .001).
• Symptomatic intracranial hemorrhage occurred in 1% of intervention patients vs 0.5% of control individuals (adjusted odds ratio, 3.10; P = .33).
• 90-day mortality was significantly higher in the intervention group than in the control group (12% vs 6%; adjusted risk difference, 5.9%; P = .03).

IN PRACTICE:

The authors of an accompanying editorial wrote, “The CHOICE-2 trial strengthens the argument that tissue-level reperfusion after thrombectomy remains a therapeutic target and that pharmacological adjunctive therapies merit serious investigation, even after technically successful recanalization. But it is not yet a practice-changing study.”

“Future studies will need to confirm not only whether adjunctive intra-arterial thrombolysis works, but in whom, under which imaging phenotype, and at what safety cost,” they added.

SOURCE:

The study was led by Arturo Renú, MD, Comprehensive Stroke Center, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain. Lead author of the accompanying editorial was Urs Fischer, MD, University Hospital Bern, University of Bern, Bern, Switzerland. Both articles were published online on May 7 in JAMA.

LIMITATIONS:

The open-label design of the study may have introduced a bias. The use of noncontrast CT imaging limited the sensitivity for accurate volumetric measurements and detection of subtle infarct progression. Incomplete documentation of screening exclusions may have introduced selection bias and limited the generalizability of the findings. The trial was conducted within a single national health system in Spain with relatively uniform standards of care, limiting generalizability to other settings. Additionally, residual baseline imbalances may have influenced the outcomes.

DISCLOSURES:

The study was funded by the Instituto de Salud Carlos III and the European Union Next Generation EU/Mecanismo Para la Recuperación y la Resiliencia/Plan de Recuperación, Transformación y Resiliencia. Funding information for the editorial was not provided. Disclosure information for the study investigators and editorial authors is provided in the original articles.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.