Late-Breaking CHOICE 2 Data Indicate Alteplase Displayed Improved Stroke Recovery

An investigator-initiated, multicenter, open-label, randomized, phase 3 CHOICE 2 trial (NCT05797792) found that adding the intra-arterial thrombolysis (IAT), alteplase, after successful endovascular thrombectomy significantly improved recovery in patients with large-vessel occlusion acute ischemic stroke.¹

Results from CHOICE 2, presented as late breaking data at the 2026 International Stroke Conference (ISC) held February 4-6, in New Orleans, Louisiana, indicated those receiving endovascular treatment (EVT) and IAT treatments showed higher excellent function outcomes (57.5%) and lower rates of inadequate blood flow to the brain in small vessels (28.6%) at 90 days compared to those just receiving EVT (42.5%; 50.5%), respectively.

Additionally, the inclusion of alteplase did not significantly increase safety risks or recovery scores. Results display patients receiving EVT and alteplase were not significantly more likely to have a brain bleed (1.4% vs. 0.5%) or have increased mortality rates (12.1% vs. 6.4%). Furthermore, patients receiving alteplase rated themselves higher on mobility, self-care, performing usual activates, and lower in lower pain or discomfort, and depression or anxiety.

“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 Angel Chamorro, M.D., Ph.D., FreeOx Biotech co-founder and professor of neurology with the Faculty of Medicine at the University of Barcelona in a statement. “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,”¹

A total of 440 patients were enrolled in the trial, and 431 were included in the modified full analysis set. Participants had a median age of 76 years with women consisting of 51% of the cohort, and white consisting of 95%. All participants had acute ischemic stroke due to large-vessel occlusion and achieved successful reperfusion (eTICI 2b50–3) after EVT.²

READ MORE: CREST-2 Substudy Shows No Cognitive Benefit of Carotid Revascularization in Asymptomatic Carotid Stenosis

Patients were randomized to receive EVT alone (N = 217) or EVT followed by adjunctive IAT (n = 214). 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.

The primary outcome was functional status at 90 days, measured by the modified Rankin Scale (mRS). Key secondary outcomes included microvascular hypoperfusion on CT perfusion (CTP) and infarct expansion ratio at follow-up. Safety outcomes included symptomatic ICH within 36 ± 24 hours of randomization and all-cause mortality.

These findings come after a 2022 study that evaluated Alteplase administration in adjunction to EVT in patients with acute ischemic stroke. the 2022 study found that Alteplase improved in-hospital mortality and functional outcomes in patients; however, there was an increased association with symptomatic intracranial hemorrhage (sICH).³

The previous study included a cohort of 10,548 patients on alteplase and 5284 with only EVT. Those with alteplase were less likely to die (11.1% vs 13.9%; adjusted odds ratio [aOR], 0.83; 95% CI, 0.77-0.89; P <.001), more likely to have no major disability based on modified Rankin scale (mRS) score of 2 or less at discharge (28.5% vs 20.7%; aOR, 1.36; 95% CI, 1.28-1.45; P <.001), and to have better reperfusion based on modified Thrombolysis in Cerebral Infarction grade 2b or better (90.9% vs 88.0%; aOR, 1.39; 95% CI, 1.28-1.50; P <.001).

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REFERENCES
1. Infusion of clot-buster medication after clot removal may improve stroke recovery. American Stroke Association. News Release. February 4. Accessed February 4, 2026. https://newsroom.heart.org/news/infusion-of-clot-buster-medication-after-clot-removal-may-improve-stroke-recovery?preview=2b3c&preview_mode=True
2. Renu A, Amaro S, Urra X, et al. The Chemical Optimization of Cerebral Embolectomy (CHOICE2) Trial: Main Results. Presented at International Stroke Conference; February 4-6; New Orleans, Louisiana.
3. Smith EE, Zerna C, Solomon N, et al. Outcomes after endovascular thrombectomy with or without alteplase in routine clinical practice. JAMA Neurol. Published online June 13, 2022. doi:10.1001/jamaneurol.2022.1413